Research recommendations

NICE research uncertainties are unanswered research questions that emerge during guidance development and published as research recommendations by NICE's research and development team.
The recommendations are developed using the NICE research recommendations interim process and methods guide, which supports NICE guidance producers in making research recommendations (for example, from identifying uncertainties to prioritising research recommendations).

As NICE does not have an annual budget for primary research, it has close engagement and arrangements with the National Institute for Health Research (NIHR) to identify and address research priorities. The engagement is carried out through regular meetings on an annual cyclical basis.

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Recommendation ID

Recommendation Name

Last Reviewed Date

CG113/1 | What is the relative effectiveness of sertraline compared with cognitive behavioural therapy (CBT) in people with generalised anxiety disorder (GAD) that has not responded to guided self-help and psychoeducation in a stepped-care model?

CG113/2 | In well-defined generalised anxiety disorder (GAD), what is the clinical and cost effectiveness of two cognitive behavioural therapy (CBT) based low-intensity interventions (CCBT and guided bibliotherapy) compared with a waiting-list control?

CG113/3 | For people with generalised anxiety disorder (GAD) who are ready to start a low-intensity intervention, what is the clinical effectiveness of physical activity compared with waiting-list control?

CG113/6 | In well-defined panic disorder, what is the clinical and cost effectiveness of two cognitive behavioural therapy (CBT) based low-intensity interventions (CCBT and guided bibliotherapy) compared with a waiting-list control?

CG114/1 | Intravenous iron in children:- A prospective study of adequate duration of intravenous iron preparations in children with anaemia of chronic kidney disease (CKD), including safety, dosing and efficacy outcomes.

CG114/2 | Trials of erythropoiesis-stimulating agents (ESAs) in children:- Trials of ESAs in children with anaemia of chronic kidney disease (CKD) (including darbepoetin, which is currently not licensed for use in children younger than 12 years) including safety, dosing and efficacy outcomes.

CG115/4 | For which service users who are moderately and severely dependent on alcohol is an assertive community treatment model a clinically and cost-effective intervention compared with standard care?

CG115/5 | For people with moderate and severe alcohol dependence who have significant comorbid problems, is an intensive residential rehabilitation programme clinically and cost effective when compared with intensive community-based care?

CG116/1 | Prevalence and natural history of non-IgE-mediated food allergy:- How common are non-IgE-mediated food allergies in children and young people in primary care and community settings and when food allergies may be outgrown?

CG116/2 | Clinical predictors of non-IgE-mediated food allergy:- Which features in the clinical history best predict the presence of non-IgEmediated food allergy in children and young people in primary care and community settings?

CG116/3 | Information needs for children and young people:- during their care pathway to diagnosis of food allergy:- What do children and young people with IgE-mediated food allergy and their parents or carers want to know during the process of diagnosis and how is this demand best met?

CG116/4 | Values of skin prick testing and specific IgE antibody testing and their predictive value:- Can skin prick testing and specific IgE antibody testing cut-off points be established to diagnose IgE-mediated food allergy in children and young people, and to predict the severity of reaction?

CG116/5 | Modes of provision of support to healthcare professionals:- What would be the impact of dietetic telephone support to healthcare professionals to aid in the diagnosis and assessment of babies showing non-IgE-mediated food allergy symptoms in primary care and community settings?

CG117/2 | Directly observed therapy:- A cluster randomised controlled trial of directly observed therapy (DOT) compared with self-administered treatment for latent and/or active tuberculosis (TB) should be conducted in a UK population. This should be targeted at homeless people, and those with a history of non-adherence, alcoholism, drug abuse or mental illness.

CG117/3 | New entrant screening and treatment for latent tuberculosis (TB) infection:- A study is needed of people found by new entrant screening to be Mantoux positive and interferon-gamma positive, to establish better estimates of the cost effectiveness of screening and treatment for latent TB infection in this population. This could identify factors predisposing people to developing active TB so that more effective targeted treatment programmes can be developed for latent TB infection.

CG117/4 | Protective effects of Bacille Calmette-Guèrin (BCG):- A case-control study is needed, comparing people who developed active or latent tuberculosis (TB) with those who did not, and comparing the proportions of people in each group who had been vaccinated and the time since vaccination. The aim will be to derive improved estimates of protective efficacy and duration of protection of the BCG vaccine.

CG117/5 | Quality of life:- A study is needed to ascertain quality-of-life score estimates from those with tuberculosis (TB) (both active disease and latent infection), including adverse treatment effects, using an appropriate quality-of-life instrument. This will improve economic decision-making throughout TB care.

CG117/6 | Contact tracing in household contacts and homeless people:- Research is needed to determine whether contact tracing is more effective (in terms of identifying cases of latent infection and active disease) among household contacts than among street homeless contacts of patients with confirmed tuberculosis (TB) (including those using direct-access hostels for the homeless).

CG117/7 | Incentives for attending new entrant screening:- Research is needed to determine whether Port of Arrival scheme referrals with incentives for attending screening identify more cases of latent tuberculosis (TB) infection and active TB disease in new entrants than Port of Arrival scheme referrals with no incentives.

CG118/1 | Surveillance programmes for people at increased risk of colorectal cancer:- How effective are colonoscopic surveillance programmes in improving overall survival and cancer-related survival in people at increased risk of colorectal cancer?

CG118/2 | Natural history of progression to colorectal cancer in people at increased risk:- What is the natural history of progression to colorectal cancer in people with inflammatory bowel disease (IBD) or adenomas?

CG118/3 | Effectiveness of biomarkers for determining level of risk of colorectal cancer:- Which biomarkers, including epigenic and genetic markers, are predictors of colorectal cancer? How should these be used to improve risk stratification?

CG119/1 | Further research should be undertaken to determine the clinical and cost effectiveness of the following therapies; negative pressure wound therapy, total contact casting, hyperbaric oxygen therapy and surgical debridement for diabetic foot problems.

CG120/1 | What are the prevalence, risk and protective factors, and course of illness for different combinations of psychosis and coexisting substance misuse (for example, schizophrenia and cannabis misuse or bipolar disorder and alcohol misuse)?

CG121/1 | Selection of patients with non-small-cell lung cancer (NSCLC) for treatment with curative intent:- Further studies should be performed into factors that predict successful outcome of treatment with curative intent. Studies should include fitness parameters and functional imaging.

CG121/2 | Effectiveness of surgery with or without multimodality treatment in N2 disease:- Patients with non-bulky single zone N2 disease should be considered for trials of surgery with or without multimodality treatment. Outcomes should include mortality and 5-year survival.

CG121/3 | Pulmonary rehabilitation, optimisation of drug treatment and enhanced recovery programmes:- Research should be undertaken into the benefits of pulmonary rehabilitation, optimisation of drug treatment and enhanced recovery programmes before and after surgery. Outcomes should include mortality, survival, pulmonary complications, pulmonary function and quality of life (including assessment by EQ-5D).

CG121/4 | New regimens for radiotherapy with curative intent:- Research should be considered into dose escalation in radiotherapy with curative intent, including stereotactic body irradiation (SBRT). Outcomes should include mortality, pulmonary complications, pulmonary function and validated quality of life measures (including assessment by EQ-5D).

CG121/5 | Imaging modalities for monitoring response and recurrent disease:- Randomised controlled trials should be conducted to examine the value of imaging modalities and other interventions in the monitoring of response and recurrent disease.

CG122/1 | Relationship between duration of symptoms of ovarian cancer and stage at diagnosis:- Further research should be undertaken on the relationship between the duration and frequency of symptoms in women with ovarian cancer before diagnosis, the stage of disease at diagnosis and subsequent survival.

CG122/2 | RMI I (risk of malignancy index I) threshold for women with suspected ovarian cancer:- Further research should be undertaken to determine the optimum RMI I threshold that should be applied in secondary care to guide the management of women with suspected ovarian cancer.

CG122/3 | Imaging in the diagnostic pathway for women with ovarian cancer:- Large multicentre case–control studies should be conducted to compare the accuracy of CT versus MRI for staging and for predicting optimal cytoreduction in women with ovarian cancer.

CG122/4 | The role of systematic retroperitoneal lymphadenectomy in the surgical treatment of ovarian cancer:- A prospective randomised trial should be undertaken to evaluate the therapeutic effect, associated risks and cost effectiveness of systematic retroperitoneal lymphadenectomy in women with ovarian cancer whose disease appears to be confined to the ovaries.

CG122/5 | The value of primary surgery for women with advanced ovarian cancer:- Research should be undertaken to determine the effectiveness of primary surgery for women with advanced ovarian cancer whose tumour cannot be fully excised.

CG123/1 | Comprehensive assessment versus a brief assessment:- For people with a suspected common mental health disorder, what is the clinical and cost effectiveness of using a comprehensive assessment (conducted by mental health professional) versus a brief assessment (conducted by a paraprofessional)?

CG123/2 | 'Walking across’ from one assessment instrument to another:- What methodology should be used to allow ‘walking across’ from one assessment instrument for common mental health disorders to another?

CG123/3 | Generalized Anxiety Disorder scale (GAD-2) for people with suspected anxiety disorders:- In people with suspected anxiety disorders, what is the clinical utility of using the GAD-2 compared with routine case identification to accurately identify different anxiety disorders? Should an avoidance question be added to improve case identification?

CG123/4 | Routine outcome measurement:- In people with a common mental health disorder, what is the clinical utility of routine outcome measurement and is it cost effective compared with standard care?

CG123/5 | Use of a simple algorithm compared with a standard clinical assessment:- For people with a common mental health disorder, is the use of a simple algorithm (based on factors associated with treatment response), when compared with a standard clinical assessment, more clinically and cost effective?

CG124/1 | Imaging options in occult hip fracture:- In patients with a continuing suspicion of a hip fracture but whose radiographs are normal, what is the clinical and cost effectiveness of computed tomography (CT) compared to magnetic resonance imaging (MRI), in confirming or excluding the fracture?

CG124/3 | Displaced intracapsular hip fractures:- What is the clinical and cost effectiveness of large-head total hip replacement versus hemiarthroplasty on functional status, reoperations and quality of life in patients with displaced intracapsular hip fracture?

CG124/5 | Early supported discharge in care home patients:- What is the clinical and cost effectiveness of early supported discharge on mortality, quality of life and functional status in patients with hip fracture who are admitted from a care home?

CG126/1 | Adding a newer anti-anginal drug to a calcium channel blocker:- What is the clinical and cost effectiveness of adding a newer anti-anginal drug (nicorandil, ivabradine or ranolazine) to a calcium channel blocker for treating stable angina?

CG126/2 | Management of stable angina in people with evidence of ischaemia on non-invasive functional testing:- Do people with stable angina and evidence of reversible ischaemia on noninvasive functional testing who are on optimal drug treatment benefit from routine coronary angiography with a view to revascularisation?

CG126/3 | Early revascularisation strategy for people with angina and multivessel disease:- In people with stable angina and multivessel disease (including left main stem disease) whose symptoms are controlled with optimal drug treatment, would an initial treatment strategy of revascularisation be clinically and cost effective compared with continued drug treatment?

CG126/4 | Cardiac rehabilitation:- Is an 8-week, comprehensive, multidisciplinary, cardiac rehabilitation service
more clinically and cost effective for managing stable angina than current clinical practice?

CG127/3 | Methods of assessing lifetime cardiovascular risk in people aged under 40 years with hypertension:- In people aged under 40 years with hypertension, what is the most accurate method of assessing the lifetime risk of cardiovascular events and the impact of therapeutic intervention on this risk?

CG128/1 | Training professionals:- Does training professionals to recognise signs and symptoms of autism lead to earlier assessment of needs and earlier diagnosis (and by implication reduce morbidity/improve health outcomes) among children and young people with suspected autism compared with no training?

CG128/2 | Gathering information in schools or nurseries:- Does routine additional information from educational settings (such as nursery or school) improve accuracy in diagnosing autism among children or young people up to the age of 19 compared with signs and symptoms alone?

CG128/4 | Comparative genomic hybridisation array:- What is the effectiveness and acceptability of comparative genomic hybridisation (CGH) array compared with current genetic testing in children and young people with identified autism?

CG129/3 | Monitoring for intrauterine growth restriction:- What is the pattern of fetal growth in healthy twin and triplet pregnancies, and how should intrauterine growth restriction be defined in twin and triplet pregnancies?

CG129/4 | Preventing preterm birth:- What interventions are effective in preventing spontaneous preterm birth in women with twin and triplet pregnancies, especially in those at high risk of preterm birth?

CG129/5 | Indications for referral to a tertiary level fetal medicine centre:- What is the incidence of monochorionic monoamniotic twin and triplet pregnancies, and what clinical management strategies are most effective in such pregnancies?

CG130/1 | Optimal management of hyperglycaemia in acute coronary syndromes (ACS): What is the optimal management of hyperglycaemia in people with acute coronary syndrome who have diagnosed or previously undiagnosed diabetes?

CG131/2 | The value of prognostic factors in guiding optimal management in patients with locally excised, pathologically confirmed stage I cancer:- An observational study should be conducted, incorporating standardised assessment of pathological prognostic factors, to assess the value of the proposed prognostic factors in guiding optimal management in patients with locally excised, pathologically confirmed stage I cancer. Outcomes of interest are disease-free survival, overall survival, local and regional control, toxicity, cost effectiveness and quality of life.

CG131/3 | The most effective sequence to perform magnetic resonance imaging (MRI and PET-CT in patients with colorectal cancer metastasised to the liver to determine whether the metastasis is resectable:- A prospective trial should be conducted to investigate the most clinically-effective and cost-effective sequence in which to perform MRI and PET-CT, after an initial CT scan, in patients with colorectal cancer that has metastasised to the liver, to determine whether the metastasis is resectable. The outcomes of interest are reduction in inappropriate laparotomies and improvement in overall survival.

CG131/4 | Follow-up after completion of oncological treatment:- Strategies to integrate oncological surveillance with optimising quality of life, reducing late effects, and detecting second cancers in survivors of colorectal cancer should be developed and explored.

CG131/5 | Patient-reported outcome measures in colorectal cancer:- Colorectal cancer-specific patient-reported outcome measures (PROMs) should be developed for use in disease management and to inform outcome measures in future clinical trials.

CG132/1 | Decision-to-delivery interval (category 1 urgency):- What factors influence the decision-to-delivery interval when there is a category 1 level of urgency for Caesarean Section (CS)?
Factors to be investigated could include:
• staff grade/level of experience
• skill mix in the multidisciplinary team
• task allocation
• methods of communication
• time of day
• availability of ongoing staff training about emergency procedures and levels of attendance.
The research could be conducted using simulation methods and video observation to determine what factors influence the decision-to-delivery interval for category 1 CS. The videos could also be used to train staff.

CG132/10 | Women should be informed that the effects on the likelihood of Caesarean Section (CS) of complementary therapies used during labour (such as acupuncture, aromatherapy, hypnosis, herbal products, nutritional supplements, homeopathic medicines, and Chinese medicines) have not been properly evaluated and further research is needed before such interventions can be recommended. [2004]

CG132/3 | National audit:- Repeat of the National Caesarean Section Sentinel Audit. The original Caesarean Section (CS) guideline included a set of 'auditable standards'. It would be a straightforward task to produce an updated set of auditable standards based on the important topics covered in the updated guideline. These could include:
• consent
• indications (including maternal request)
• procedural aspects
• maternal and fetal outcomes.
Many of the outcomes documented in a new CS audit would relate directly to recommendations in this CS guideline update. Researchers may also want to consider categorising different reasons underlying maternal request for CS such as previous poor childbirth experience, longstanding fear of childbirth, belief that CS is safer for the baby etc.
An additional useful feature of the audit would be to record key related data, such as the proportion of CS deliveries for a breech presentation that had an attempted external cephalic version.

CG132/4 | Maternal request for Casarean Section (CS): What support or psychological interventions would be appropriate for women who have a fear of vaginal childbirth and request a CS?
Interventions for evaluation could include:
• support from a named member of the maternity team
• continuity of carer
• formal counselling
• cognitive behavioural therapy.
Outcomes could include:
• mode of birth planned at term
• psychological outcomes (postnatal depression, post-traumatic stress disorder, self-esteem, mother–infant bonding)
• breastfeeding.

CG132/5 | Risks and benefits of Caesarean Section (CS): What are the medium- to long-term risks and benefits to women and their babies of planned CS compared with planned vaginal birth? The main focus would be the outcomes in women, which could be measured at 1 year (medium term) and 5–10 years (long term). These outcomes could include:
• urinary dysfunction
• gastrointestinal dysfunction
• dyspareunia
• breastfeeding
• psychological health.
Infant outcomes could include medical problems, especially ongoing respiratory and neurological problems.

CG132/6 | In otherwise uncomplicated twin pregnancies at term where the presentation of the first twin is cephalic, perinatal morbidity and mortality is increased for the second twin. However, the effect of planned Caesarean Section (CS) in improving outcome for the second twin remains uncertain and therefore CS should not routinely be offered outside a research context. [2004]

CG132/7 | Preterm birth is associated with higher neonatal morbidity and mortality. However, the effect of planned Caesarean Section (CS) in improving these outcomes remains uncertain and therefore CS should not routinely be offered outside a research context. [2004]

CG132/8 | The risk of neonatal morbidity and mortality is higher with 'small for gestational age' babies. However, the effect of planned Caesarean Section (CS) in improving these outcomes remains uncertain and therefore CS should not routinely be offered outside a research context. [2004]

CG132/9 | Pregnant women with a recurrence of herpes simplex virus (HSV) at birth should be informed that there is uncertainty about the effect of planned Caesarean Section (CS) in reducing the risk of neonatal HSV infection. Therefore, CS should not routinely be offered outside a research context. [2004]

CG133/1 | Effectiveness of training:- For healthcare professionals who work with people who self-harm, does the provision of training in assessment and management improve outcomes compared with no additional specialist training?
A well-powered randomised controlled trial should examine the effectiveness of training. Researchers should consider the format and length of training. The outcomes chosen should include both healthcare professionals' and service users' evaluation of the training, and the effect on subsequent knowledge, attitude and behavioural changes. It should include longer-term follow-up of 12 months or more.

CG133/2 | Effectiveness of psychosocial assessment with a valid risk scale:- For people who self-harm (including young people), does the provision of psychosocial assessment with a validated risk scale, compared with psychosocial assessment alone, improve outcomes?
This question should be answered using a well-conducted randomised controlled trial. The assessment should be conducted by mental health professionals in community mental health teams. The main outcomes should include both hospital-reported and self-reported repetitions of self-harm. Outcomes such as service users' experience of assessment and the impact on therapeutic engagement should also be included. The duration of the study should be at least 6 months.

CG133/3 | Clinical and cost effectiveness of psychological therapy:- with problem-solving elements for people who self-harm:- For people who have self-harmed, does the provision of a psychological therapy with problemsolving elements, compared with treatment as usual, improve outcomes? What is the differential effect for people with a past history of self-harm, compared with people who self-harm for the first time? This question should be answered using a well-conducted randomised controlled trial. Consider six sessions of psychological therapy with problem-solving elements, delivered immediately after discharge for the index episode of self-harm. The therapist should be trained and experienced in working with people who self-harm. Participants' history of previous self-harm, methods used and psychiatric history should be noted. Primary outcomes should include both hospital-reported and self-reported repetitions of self-harm. Other important outcomes, such as quality of life, depressive symptoms, service users' experience and adverse events (for example, distress or exacerbation of symptoms associated with therapy) should be included. The study design should take into account the complex motives that underpin self-harm. Studies need to be large enough to determine the intervention's costs and cost effectiveness.

CG133/4 | Clinical effectiveness of low-intensity/brief psychosocial interventions for people who self-harm:- For people who self-harm, does the provision of potentially cheap low-intensity/brief psychosocial interventions, compared with treatment as usual, improve outcomes? This question should be answered using a well-conducted randomised controlled trial. Consider using a variety of approaches, including postcards, emergency cards, phone calls, or the use of electronic media in community mental health settings. The outcomes should include service users' engagement and experience, and hospital-reported and self-reported repetitions of self harm. Other important outcomes, such as quality of life, depressive symptoms and adverse events (for example, distress or exacerbation of symptoms associated with contact with services) should be included.

CG133/5 | Observational study exploring different harm-reduction approaches:- What are the different approaches to harm reduction following self-harm in NHS settings?
A study should be carried out to investigate the different approaches to harm reduction following self-harm currently in use in NHS settings. This could use survey methodology with all, or a selected sample of, mental health service providers. Audit data should be used to provide a preliminary evaluation of potential utility. Promising interventions might be tested in small-scale pilot randomised controlled trials, which use frequency and severity of self-harm, and standard measures of distress and psychological symptoms, as outcome measures. Other outcomes such as quality of life, service users' experience and adverse events should be included.

CG134/2 | The frequency and effects of biphasic reactions:- What are the frequency, timing, severity and predictors of biphasic reactions in people who have received emergency treatment for anaphylaxis?

CG134/5 | Effect of specialist services on health-related quality of life:- For people who have experienced suspected anaphylaxis, what is the effect on health-related quality of life of (a) referral to specialist allergy services and (b) provision of adrenaline injectors, when compared with emergency treatment alone?

CG136/1 | Training in the use of the national quality standard and guidance on service user experience of care:- For people using adult mental health services, what is the effect of training community mental health teams (CMHTs) and inpatient ward staff in the use of the national quality standard and underpinning guidance on service user experience, when compared to no training, on service
users' experience of care?

CG136/2 | Late access to services and compulsory and intensive treatment:- For people using adult mental health services, what are the personal and demographic factors associated with late access to services and an increased likelihood of compulsory and intensive treatment, and what are the key themes that are associated with poor engagement? This should include an examination of factors that impact on access to services among younger people and older adults.

CG136/3 | Shared decision-making:- For people using adult mental health services, what are the key aspects of 'shared decision-making' that they prefer, and does a training programme for health and social care professionals designed around these key aspects, when compared with no training, improve service users' experience of care? A study should be undertaken to evaluate the impact on treatment choice, the experience of care and treatment effectiveness of training service users to deal with health and social care professionals assertively.

CG136/5 | Compulsion, control and restraint:- For people using adult mental health services, how is compulsory treatment and 'control and restraint' used in different settings and what is the impact on the service user?

CG137/2 | Epilepsy syndromes:- What are the initial and add-on anti-epileptic drugs (AEDs) of choice in the treatment of the epilepsy syndromes with onset in childhood, for example, myoclonic-astatic epilepsy and Dravet syndrome?

CG137/3 | Infantile spasms:- Does treatment response relate to cause in infantile spasms? Does early treatment success in seizure control and resolution of the hypsarrhythmic electroencephalogram (EEG) influence the long-term developmental and cognitive outcomes more than the underlying cause of the spasms?

CG139/1 | Standard principles of infection prevention and control:- What are the barriers to compliance with the standard principles of infection prevention and control that patients and carers experience in their own homes?

CG139/2 | Hand decontamination:- When clean running water is not available, what is the clinical and cost effectiveness of using wipes, gels, handrubs or other products to remove visible contamination?

CG139/5 | Indwelling urinary catheters: antibiotic prophylaxis:- When recatheterising patients who have a long-term indwelling urinary catheter, what is the clinical and cost effectiveness of single-dose antibiotic prophylaxis in reducing symptomatic urinary tract infections in patients with a history of urinary tract infections associated with catheter change?

CG140/1 | Communication:- What are the most clinically effective and cost-effective methods of addressing patient and carer concerns about strong opioids, including anticipating and managing adverse effects, and engaging patients in prescribing decisions?

CG140/2 | Side effects:- Is prophylactic prescription of anti-emetic treatment or availability of anti-emetic treatment at the patient's home more effective in reducing nausea than the availability of prescription on request for patients starting strong opioids for the treatment of pain in advanced or progressive disease? The outcomes of interest are nausea, time to control of nausea, patient acceptability of treatment, concordance and use of healthcare resources.

CG140/3 | Side effects:- Is early switching of opioid, on development of side effects, more effective at reducing central side effects than persisting with current opioid and dose reduction in patients starting strong opioids? The outcomes of interest are time to clinically effective pain control with acceptable side effects.

CG142/1 | Facilitated self-help for anxiety and depression in adults with autism:- What is the clinical and cost effectiveness of facilitated self-help for the treatment of mild anxiety and depressive disorders in adults with autism?

CG142/2 | Cognitive behavioural therapy (CBT) for anxiety disorders in adults with autism:- What is the clinical and cost effectiveness of CBT for the treatment of moderate and severe anxiety disorders in adults with autism?

CG142/3 | Pharmacological treatments for depression in adults with autism:- What is the clinical and cost effectiveness of selective serotonin reuptake inhibitors (SSRIs) for the treatment of moderate and severe depression in adults with autism?

CG143/1 | Pain management for patients with an acute painful sickle cell episode:- For patients with an acute painful sickle cell episode, what are the effects of different opioid formulations, adjunct pain therapies and routes of administration on pain relief and acute sickle cell complications?

CG143/2 | Use of low-molecular-weight heparin to treat patients with an acute painful sickle cell episode:- Are therapeutic doses of low-molecular-weight heparin (LMWH) effective, compared with prophylactic doses of LMWH, in reducing the length of stay in hospital of patients with an acute painful sickle cell episode?

CG143/4 | Non-pharmacological interventions for patients with an acute painful sickle cell episode:- For patients with an acute painful sickle cell episode, are non-pharmacological interventions, such as massage, effective in improving their recovery from the episode?

CG144/1 | Diagnosis of deep vein thrombosis:- What is the clinical and cost effectiveness of a whole-leg ultrasound scan compared with a proximal leg vein ultrasound scan in the diagnosis of acute deep vein thrombosis (DVT)?

CG144/2 | Long-term versus 3-month oral anticoagulation treatment in subgroups of patients at increased risk of VTE recurrence:- What is the clinical and cost effectiveness of long-term oral anticoagulation treatment in specific subgroups of patients with a first unprovoked VTE?

CG144/3 | Long-term anticoagulation treatment with low molecular weight heparin versus a vitamin K antagonist in patients with VTE and active cancer:- In patients with VTE and active cancer who have had 6 months of anticoagulation treatment with low molecular weight heparin (LMWH), what is the clinical benefit (in terms of VTE recurrence rates, all-cause mortality and major bleeding) and cost effectiveness of continued anticoagulation treatment with LMWH versus a vitamin K antagonist (VKA)?

CG144/4 | Thrombolytic therapy for DVT:- What is the clinical and cost effectiveness of clot removal using catheter-directed thrombolytic therapy or pharmacomechanical thrombolysis compared with standard anticoagulation therapy for the treatment of acute proximal DVT?

CG144/5 | Systemic pharmacological thrombolysis compared with standard anticoagulation treatment in patients with pulmonary embolism and right ventricular dysfunction:- What is the clinical and cost effectiveness of systemic pharmacological thrombolysis compared with standard initial anticoagulation therapy in patients with confirmed PE and haemodynamic stability who present with right ventricular dysfunction?

CG145/3 | Botulinum toxin type A:- What is the clinical and cost effectiveness of botulinum toxin type A when used routinely or according to clinical need in children and young people who are at Gross Motor Function Classification System (GMFCS) level I, II or III?

CG145/4 | Intrathecal baclofen:- What is the clinical and cost effectiveness of continuous pump-administered intrathecal baclofen compared with usual care in children and young people who are at Gross Motor Function Classification System (GMFCS) level IV or V?

CG145/5 | Selective dorsal rhizotomy:- Does selective dorsal rhizotomy followed by intensive rehabilitation performed between the ages of 3 and 9 years in children who are at Gross Motor Function Classification System (GMFCS) level II or III result in good community mobility as a young adult?

CG146/1 | Using GP practice lists to identify people at high risk:- What is the clinical and cost effectiveness of using GP practice lists to identify people at high risk of fracture, leading to formal risk assessment and possible treatment?

CG146/3 | FRAX and QFracture in adults with secondary causes of osteoporosis:- What is the utility of FRAX and QFracture in detecting risk of fragility fracture in adults with secondary causes of osteoporosis?

CG147/1 | Angioplasty versus bypass surgery for treating people with critical limb ischaemia caused by disease of the infra-geniculate arteries:- What is the clinical and cost effectiveness of a 'bypass surgery first' strategy compared with an 'angioplasty first' strategy for treating people with critical limb ischaemia caused by disease of the infra-geniculate (below the knee) arteries?

CG147/2 | Supervised exercise programmes for treating people with intermittent claudication:- What is the clinical and cost effectiveness of supervised exercise programmes compared with unsupervised exercise for treating people with intermittent claudication, taking into account the effects on long-term outcomes and continuing levels of exercise?

CG147/3 | Patient attitudes and beliefs about peripheral arterial disease:- What is the effect of people's attitudes and beliefs about their peripheral arterial disease on the management and outcome of their condition?

CG147/4 | Primary versus secondary stenting for treating people with critical limb ischaemia caused by disease of the infra-geniculate arteries:- What is the clinical and cost effectiveness of selective stent placement compared with angioplasty plus primary stent placement for treating people with critical limb ischaemia caused by disease of the infra-geniculate arteries?

CG147/5 | Chemical sympathectomy for managing critical limb ischaemic pain:- What is the clinical and cost effectiveness of chemical sympathectomy in comparison with other methods of pain control for managing critical limb ischaemic pain?

CG148/1 | Safety and efficacy of antimuscarinics:- What is the safety and efficacy of more recently developed antimuscarinics compared with (a) placebo/usual care and (b) other antimuscarinics in the treatment of neurogenic lower urinary tract dysfunction?

CG148/2 | Safety and efficacy of botulinum toxin:- What is the safety and efficacy of botulinum toxin compared with (a) usual care, (b) antimuscarinics and (c) augmentation cystoplasty in people with neurogenic lower urinary tract dysfunction?

CG148/3 | Management strategies to reduce the risk of symptomatic urinary tract infections:- In people with neurogenic lower urinary tract dysfunction, which management strategies (including the use of prophylactic antibiotics and various invasive and non-invasive techniques to aid bladder drainage) reduce the risk of symptomatic urinary tract infections?

CG148/4 | Bladder management strategies:- What are the long-term risks and effects on quality of life of different bladder management strategies for lower urinary tract dysfunction in people with neurological disease?

CG148/5 | What is the safety and efficacy of botulinum toxin compared with (a) usual care, (b) antimuscarinics and (c) augmentation cystoplasty in people with primary cerebral conditions with lower urinary tract dysfunction?

CG149/1 | Screening and intrapartum antibiotic prophylaxis for group B streptococcal colonisation:- What is the clinical and cost effectiveness of intrapartum antibiotic prophylaxis targeting group B streptococcus and guided by routine antenatal screening?

CG149/2 | Risk factors for early-onset neonatal infection and symptoms and signs:- Which risk factors for early-onset neonatal infection, clinical symptoms and signs of infection, and laboratory investigations should be used to identify babies who should receive antibiotics?

CG149/4 | Investigations during antibiotic treatment:- What is the clinical and cost effectiveness of laboratory investigations used individually or in combination to exclude early-onset neonatal infection in babies receiving antibiotics for suspected infection?

CG150/4 | Psychological interventions to manage chronic headache disorders:- Does a psychological intervention such as cognitive behavioural therapy (CBT) improve headache outcomes and quality of life for people with chronic headache disorders?

CG150/5 | Pharmacological treatments for headache prophylaxis to aid withdrawal treatment in medication overuse
headache:- Does a course of steroid treatment or pharmacological treatments used for headache prophylaxis help people with medication overuse headaches withdraw from medication?

CG151/1 | Service provision for neutropenic sepsis in patients with cancer:- A prospective national cohort study should be carried out to assess the incidence of suspected and proven neutropenic sepsis in patients having anticancer treatment.

CG151/2 | Patient support and information:- A descriptive study involving patients who have had neutropenic sepsis and their carers should be undertaken to find out what types of support and information patients and carers were given, which of these they found helpful or unhelpful, and whether they think additional or different types of support or information are needed.

CG151/3 | Signs and symptoms that predict neutropenic sepsis in the community:- A prospective study should be carried out to determine which signs and symptoms experienced by patients in the community predict neutropenic sepsis and the outcomes of these episodes.

CG151/4 | Reducing the risk of complications of anticancer treatment in children and young people, and in adults diagnosed with lymphoma:- Randomised studies should investigate primary prophylaxis of neutropenic sepsis in 2 populations: children and young people (aged under 18) having treatment for solid tumours or haematological malignancies, or stem cell transplantation; and adults (aged 18 and older) diagnosed with lymphoma. The studies should compare the effectiveness of fluoroquinolone antibiotics given alone, fluoroquinolone antibiotics given together with G-CSF preparations, and G-CSF preparations given alone. Outcome measures should include overall mortality, infectious episodes and adverse events. In addition, quality of life should be determined using quantitative and qualitative methods. The resulting data should be used to develop a cost-effectiveness analysis comparing these 3 forms of prophylaxis in children and young people having anticancer treatment, and in adults diagnosed with lymphoma.

CG151/5 | Switching from inpatient intravenous to outpatient oral antibiotic therapy in patients with neutropenic sepsis:- A randomised controlled trial should be undertaken to evaluate the clinical and cost effectiveness of stopping intravenous antibiotic therapy and switching to oral therapy within the first 24 hours of treatment in patients with neutropenic sepsis who are having treatment with intravenous antibiotics. The outcomes to be measured are overtreatment, death, need for critical care, length of hospital stay, duration of fever and quality of life.

CG152/1 | Azathioprine:- For patients with intestinal Crohn's disease, does the addition of azathioprine to glucocorticosteroid treatment at diagnosis improve the long-term outcome compared with glucocorticosteroid treatment alone?

CG152/4 | Surgery versus medical treatment for the distal ileum:- What is the effect on quality of life of medical treatment (immunosuppressive or biological therapy) compared with early surgery for Crohn's disease limited to the distal ileum?

CG152/5 | Patient information and support:- What are the information needs of people with Crohn's disease, as defined by people with the condition, and can education and support based on these needs lead to better clinical and quality of life outcomes?

CG153/1 | Assessment of disease severity and impact:- In children, young people and adults with psoriasis, can tools be developed and/or existing ones further refined and validated to:
- assess disease severity and impact in both non-specialist and specialist healthcare settings, to facilitate assessment, appropriate referral, treatment planning and measurement of outcomes
- measure burden and cumulative effect of disease activity, severity and impact for people with both psoriasis and psoriatic arthritis?

CG153/2 | Methotrexate and risk of hepatotoxicity:- What is the impact of methotrexate compared with other approaches to care (for example other systemic non-biological or biological treatments) on risk of significant liver disease in people with psoriasis and do risk factors such as obesity, alcohol use or diabetes alter this risk?

CG153/3 | Rapid escalation to systemic treatments:- In people with psoriasis, does early intervention with systemic treatments improve the long-term prognosis of psoriasis severity, comorbidities (including psoriatic arthritis), or treatment -related adverse effects, and are there any clinical (for example demographic or phenotypic) or laboratory (for example genetic or immune) biomarkers that can be used to identify those most likely to benefit from this treatment approach?

CG153/5 | Topical therapy:- In people of all ages with psoriasis: 1. How should topical therapies be used to maintain disease control i) safely; ii) effectively and iii) what are the health economic implications?
2. What are the risks of 'real life' long term corticosteroid use, are there particular people at risk
and what strategies can be used to modify or avoid risks?

CG154/1 | Early pregnancy assessment units:- A national evaluation of early pregnancy assessment unit service provision should be carried out to identify factors affecting outcomes. Factors should include whether care is provided in a dedicated unit, staffing configuration and opening hours of dedicated services. Outcomes should include both process (service) outcomes and pregnancy-related outcomes. Data collected should be used to analyse the cost effectiveness of early pregnancy assessment units compared with other models of care.

CG154/2 | Ultrasound for determining a viable intrauterine pregnancy:- How does the timing and frequency of ultrasound examination affect diagnosis and outcomes of early pregnancy complications, including women's experience and cost effectiveness?

CG154/4 | Management of miscarriage:- In women with confirmed miscarriage, does the type of management strategy (expectant, medical and surgical) impact on women's experience, including psychological and emotional outcomes?

CG154/5 | Surgical compared with medical management of ectopic pregnancy:- In women with ectopic pregnancy, does the type of intervention (laparoscopy or medical management) impact on women's experience, including psychological and emotional outcomes?

CG155/1 | What are the long-term outcomes, both psychotic and nonpsychotic, for children and young people with attenuated or transient psychotic symptoms suggestive of a developing psychosis, and can the criteria for 'at risk states' be refined to better predict those who will and those who will not go on to develop psychosis?

CG155/3 | What is the clinical and cost effectiveness for family intervention combined with individual CBT in the treatment of children and young people considered to be at high risk of developing psychosis and their parents or carers?

CG155/4 | What is the clinical and cost effectiveness of psychological intervention alone, compared with antipsychotic medication and compared with psychological intervention and antipsychotic
medication combined, in young people with first episode psychosis?

CG155/6 | What is the most effective management strategy for preventing the development of excessive weight gain and metabolic syndrome associated with the use of antipsychotic medication in children and
young people?

CG156/3 | Adjuvant luteal phase support treatments in IVF:- Further research is needed to assess the efficacy of adjuvant luteal phase support treatments such as low-dose aspirin, heparin, prednisolone, immunoglobulins and/or fat emulsions.

CG156/4 | Long-term safety of ovarian stimulation and ovulation induction for women:- Is there an association between ovulation induction or ovarian stimulation and adverse long-term (over 20 years) effects in women in the UK?

CG156/5 | Long-term effects of IVF with or without intracytoplasmic sperm injection in children:- What are the long-term (over 20 years) effects of IVF with or without intracytoplasmic sperm injection (ICSI) in children in the UK?

CG156/6 | People who are concerned about their fertility should be informed that the effectiveness of complementary therapies for fertility problems has not been properly evaluated and that further research is needed before such interventions can be recommended. [2004]

CG156/7 | The effectiveness of pulsatile gonadotrophin-releasing hormone in women with clomifene citrate-resistant polycystic ovary syndrome is uncertain and is therefore not recommended outside a research context. [2004]

CG157/1 | Phosphate binders in adults with chronic kidney disease (CKD) stage 4 or 5:- Which binders are most effective in controlling serum phosphate in adults with stage 4 or 5 CKD who are not on dialysis?

CG157/2 | Effectiveness and safety of aluminium hydroxide in adults:- In adults with stage 4 or 5 chronic kidney disease (CKD), including those on dialysis, what is the long-term effectiveness and safety of aluminium hydroxide in controlling serum phosphate?

CG157/3 | Effectiveness and safety of magnesium carbonate in adults:- In adults with stage 4 or 5 chronic kidney disease (CKD), including those on dialysis, what is the long-term effectiveness and safety of magnesium carbonate in controlling serum phosphate?

CG157/5 | Sequencing and combining of phosphate binders in adults:- For adults with stage 4 or 5 chronic kidney disease (CKD), including those on dialysis, what is the most effective sequence or combination of phosphate binders to control serum phosphate?

CG158/1 | Parent training programmes for children aged 12 years and over with a conduct disorder:- What is the effectiveness of parent training programmes for conduct disorders in children and young people aged 12 years and over?

CG158/3 | Maintaining the benefits of treatment and preventing relapse after successful treatment for conduct disorder:- What is the effectiveness of interventions to maintain the benefits of treatment and prevent relapse after successful treatment for conduct disorder?

CG158/4 | Combining treatment for mental health problems in parents with treatment for conduct disorders in their
children:- What is the efficacy of combining treatment for mental health problems in parents with treatment for conduct disorders in their children?

CG159/1 | Adults' uptake of and engagement with interventions for social anxiety disorder:- What methods are effective in improving uptake of and engagement with interventions for adults with social anxiety disorder?

CG159/2 | Specific versus generic CBT for children and young people with social anxiety disorder:- What is the clinical and cost effectiveness of specific CBT for children and young people with social anxiety disorder compared with generic anxiety-focused CBT?

CG159/3 | The role of parents in the treatment of children and young people with social anxiety disorder:- What is the best way of involving parents in the treatment of children and young people (at different stages of development) with social anxiety disorder?

CG159/4 | Individual versus group CBT for children and young people with social anxiety disorder:- What is the clinical and cost effectiveness of individual and group CBT for children and young people with social anxiety disorder?

CG159/5 | Combined interventions for adults with social anxiety disorder:- What is the clinical and cost effectiveness of combined psychological and pharmacological interventions compared with either intervention alone in the treatment of adults with social anxiety disorder?

CG160/3 | Diagnosis:- NICE recommends that a UK study of the performance characteristics and cost-effectiveness
of procalcitonin versus C-reactive protein in identifying serious bacterial infection in children with fever without apparent source be carried out. [2007]

CG160/4 | Antipyretics:- NICE recommends that studies are conducted in primary care and secondary care to
determine whether examination or re-examination after a dose of antipyretic medication is of
benefit in differentiating children with serious illness from those with other conditions. [2007]

CG161/1 | Environmental adaptations aimed at reducing the risk of falling in older inpatients:- What environmental adaptations can be made in existing inpatient units, and should be considered when inpatient units are built, to reduce the risk of falls and injuries in older inpatients?

CG161/2 | Prevalence of risk factors for falling in older inpatients:- Which risk factors for falling that can be treated, improved or managed during the hospital stay are most prevalent in older patients who fall in inpatient settings in the UK?

CG161/4 | Interventions for preventing falls in older inpatients:- How can falls among older inpatients be prevented? Which patients are most likely to benefit from falls prevention interventions, and does the effectiveness of interventions relate to the patient's length of stay?

CG162/1 | Upper limb electrical stimulation:- What is the clinical and cost effectiveness of electrical stimulation (ES) as an adjunct to rehabilitation to improve hand and arm function in people after stroke, from early rehabilitation through to use in the community?

CG162/2 | Intensive rehabilitation after stroke:- In people after stroke what is the clinical and cost effectiveness of intensive rehabilitation (6 hours per day) versus moderate rehabilitation (2 hours per day) on activity, participation and quality of life outcomes?

CG162/3 | Neuropsychological therapies:- Which cognitive and which emotional interventions provide better outcomes for identified subgroups of people with stroke and their families and carers at different stages of the stroke pathway?

CG162/4 | Shoulder pain:- Which people with a weak arm after stroke are at risk of developing shoulder pain? What management strategies are effective in the prevention or management of shoulder pain of different aetiologies?

CG163/1 | Broncholalveolar lavage in the diagnosis of idiopathic pulmonary fibrosis:- What is the value of bronchoalveolar lavage in people in whom idiopathic pulmonary fibrosis is considered the most likely diagnosis when clinical and CT findings are insufficient to support a confident diagnosis?

CG163/2 | Surgical lung biopsy in the diagnosis of idiopathic pulmonary fibrosis:- What is the value of surgical lung biopsy in people in whom idiopathic pulmonary fibrosis is considered the most likely diagnosis when clinical and CT findings are insufficient to support a confident diagnosis?

CG164/1 | Carrier probability calculation models:- Further research is recommended into developing and validating models for calculating carrier probability, which incorporate additional data, such as the molecular pathology of tumours and the prevalence of mutations in different ethnic groups. [new 2013]

CG164/2 | Rapid genetic testing:- Research is recommended to determine the benefits and harms of creating rapid access to genetic testing for people with newly diagnosed breast cancer. This research should address the optimum model for service delivery and organisation, the clinical and cost effectiveness of such a change, uptake outcomes and patients' experience. [new 2013]

CG164/3 | Benefits of MRI surveillance in women over 50 years:- Research is recommended to establish the risk and benefits of MRI surveillance compared with mammography in women over 50 years with a personal history of breast cancer. Studies should include sub-analysis for breast density. [new 2013]

CG164/4 | Chemoprevention to reduce incidence of breast cancer:- A randomised controlled trial is recommended to compare the clinical and cost effectiveness of aromatase inhibitors and tamoxifen for reducing the incidence of breast cancer in women with a family history of breast or ovarian cancer. [new 2013]

CG164/5 | Impact of risk-reducing surgery:- Further research is recommended to compare psychosocial and clinical outcomes in women who choose and women who do not choose to have risk-reducing surgery. [new 2013]

CG165/2 | ALT values for children and young people:- Further research should be undertaken to examine whether the upper limit of normal ALT values for adults (below 30 IU/ml for males and below 19 IU/ml for females) are appropriate for use in children and young people with chronic hepatitis B when making decisions on when to initiate treatment.

CG165/3 | Long-term safety of tenofovir disoproxil in chronic hepatitis B:- Further research should be undertaken to determine the long-term safety of tenofovir disoproxil, including the risk of clinically significant hypophosphataemia and related bone toxicity, in people with chronic hepatitis B. The cost effectiveness of routine monitoring for phosphate loss and bone disease in people with chronic hepatitis B who are receiving tenofovir disoproxil treatment needs further evaluation.

CG165/4 | Prophylactic treatment in people receiving immunosuppressive therapy:- Further research should be undertaken to determine whether long-term use of mild immunosuppressive agents for autoimmune and allergic problems presents a risk for reactivation of HBV infection in people with previous or current chronic hepatitis B, including occult HBV infection. The cost effectiveness of routine tests for HBV in this population, including HBV DNA for occult HBV infection, and the need for prophylactic treatment with nucleoside or nucleotide analogues needs further evaluation.

CG166/1 | Induction of remission for people with moderate ulcerative colitis: prednisolone compared with
aminosalicylates:- What is the clinical and cost effectiveness of prednisolone compared with aminosalicylates for the induction of remission for people with moderate ulcerative colitis?

CG166/2 | Induction of remission for people with moderate ulcerative colitis: prednisolone compared with
beclometasone:- What is the clinical and cost effectiveness of prednisolone plus an aminosalicylate compared with beclometasone plus an aminosalicylate for induction of remission for people with moderate ulcerative colitis?

CG166/3 | Induction of remission for people with subacute ulcerative colitis that is refractory to systemic corticosteroids:- What are the benefits, risks and cost effectiveness of methotrexate, ciclosporin, tacrolimus, adalimumab and infliximab compared with each other and with placebo for induction of remission for people with subacute ulcerative colitis that is refractory to systemic corticosteroids?

CG166/4 | Maintenance treatment for people with mild to moderate ulcerative colitis:- What is the clinical and cost effectiveness of regular maintenance treatment compared with no regular treatment (but rapid standard treatment if a relapse occurs) in specific populations with mild to moderate ulcerative colitis?

CG166/5 | Risk tool for predicting the likelihood of needing surgery for adults with acute severe ulcerative colitis:- To develop and validate a risk tool that predicts the likelihood of needing surgery for adults admitted to hospital with acute severe ulcerative colitis.

CG167/1 | Primary PCI and fibrinolysis in people with acute STEMI who present very early:- If a person with acute STEMI presents within 1 hour of the onset of symptoms, is it better for that person to be given fibrinolysis with a short call to needle time rather than to be transferred to a centre that carries out primary PCI for primary PCI with a delay of up to 120 minutes?

CG167/2 | Primary PCI and fibrinolysis in people with acute STEMI who have a long anticipated transfer time for primary PCI:- In people with acute STEMI who present more than 1 hour after the onset of symptoms, is a primary PCI-related delay of 120–180 minutes associated with outcomes similar to, better or worse than pre-hospital administered fibrinolysis?

CG167/4 | Culprit vessel primary PCI versus multivessel PCI:- Does multivessel PCI, at the time of presentation of people with acute STEMI, confer an advantage over a strategy of 'culprit vessel only' primary PCI, followed by further elective revascularisation driven by symptoms and evidence of ischaemia?

CG168/1 | Natural history of varicose veins:- In people with varicose veins at CEAP (Clinical, etiological, anatomical and pathophysiological) stage C2 or C3, what are the factors that influence progression of the disease to CEAP stages C5 or C6?

CG168/3 | Compression after interventional treatment:- What is the clinical and cost effectiveness of compression bandaging or hosiery after interventional treatment for varicose veins compared with no compression? If there is benefit, how long should compression bandaging or hosiery be worn for?

CG168/5 | Optimal interventional and conservative treatments at different stages of disease:- What is the optimal treatment (compression, surgery, endothermal ablation or foam sclerotherapy) for varicose veins at each of the CEAP stages, that is CEAP stages 2–3, CEAP stage 4 and CEAP stages 5–6?

CG169/3 | Definition of acute kidney injury – system for staging and detection:- Can a simplified definition and staging system, based on Système International (SI) units, be used to predict short- to medium-term outcomes in acute kidney injury?

CG169/4 | Introducing renal replacement therapy:- What is the clinical and cost effectiveness of early versus later introduction of renal replacement therapy in patients with acute kidney injury stages 2 and 3, when there is no urgent need for therapy?

CG169/5 | Preventing deterioration:- What is the clinical and cost effectiveness of continuing ACE inhibitor or ARB treatment, versus stopping treatment 24 hours before cardiac surgery and resuming 24 hours after, in people with chronic kidney disease and an eGFR of less than 30 ml/min/1.73 m2?

CG170/1 | A key worker approach for children and young people with autism and their families:- What is the value of a key worker approach (defined by protocol and delivered in addition to usual care) for children and young people with autism in terms of parental satisfaction, functioning and stress and child psychopathology?

CG170/2 | Managing behaviour that challenges in children and young people with autism:- Is a group-based parent training intervention for parents or carers of children and young people with autism clinically and cost effective in reducing early and emerging behaviour that challenges in the short- and medium-term compared with treatment as usual?

CG170/3 | Managing sleep problems in children with autism:- Is a sleep hygiene intervention or melatonin clinically and cost effective in the management of sleep onset, night waking and reduced total sleep in children (aged 4–10 years) with autism?

CG170/4 | Treating comorbid anxiety in children and young people with autism:- What is the comparative clinical and cost effectiveness of pharmacological and psychosocial interventions for anxiety disorders in children and young people with autism?

CG170/5 | Teacher-, parent- and peer-mediated psychosocial interventions in pre-school children with autism:-
Are comprehensive early interventions that combine multiple elements and are delivered by parents and teachers (for example, the Learning Experiences – an Alternative Program for Preschoolers and their Parents [LEAP] model) effective in managing the core symptoms of autism and coexisting difficulties (such as adaptive behaviour and developmental skills) in pre-school children?

CG171/1 | Pelvic floor muscle training:- How effective are different pelvic floor muscle training regimens in the management of women with overactive bladder (OAB) symptoms and to whom should it be offered?

CG171/2 | Neurostimulation:- What is the comparative effectiveness and cost-effectiveness of transcutaneous stimulation of the sacral nerve roots, and transcutaneous and percutaneous posterior tibial nerve stimulation for the treatment of OAB?

CG171/3 | Botulinum toxin A:- What is the long-term effectiveness, optimal dose and optimal frequency of repeat therapy of botulinum toxin A in women with OAB based on detrusor overactivity including risk of adverse events such as urinary infection and intermittent catheterisation?

CG171/4 | Sequence of invasive OAB procedures:- What is the effectiveness and optimum sequence of treatment with botulinum toxin A and percutaneous sacral nerve stimulation for the treatment of OAB after failed conservative (including drug) management?

CG172/3 | Is treatment with an oral anticoagulant, aspirin and clopidogrel preferable to treatment with an oral
anticoagulant and clopidogrel in people who have had an MI, have an indication for oral anticoagulation and are treated either medically, by primary PCI or by coronary artery bypass grafting surgery?

CG172/5 | In people who have had a STEMI who undergo primary PCI with a bare-metal stent, and 4 weeks of aspirin and clopidogrel, is there an additional benefit to continuing clopidogrel for a further 11 months?

CG173/2 | Relationship between symptoms, cause of neuropathic pain and its treatment:- Is response to pharmacological treatment predicted more reliably by underlying aetiology or by symptom characteristics?

CG173/3 | Carbamazepine for treating trigeminal neuralgia:- What is the clinical and cost effectiveness of carbamazepine as initial treatment for trigeminal neuralgia compared with other pharmacological treatments?

CG173/4 | Factors affecting participation and quality of life:- What are the key factors, including additional care and support, that influence participation and quality of life in people with neuropathic pain?

CG173/5 | Impact of drug-related adverse effects on cost effectiveness and quality of life:- What is the impact of drug-related adverse effects on health economics and quality of life in neuropathic pain?

CG174/3 | IV fluid therapy for fluid resuscitation:- Are balanced crystalloids superior to a combination of a balanced crystalloid and a gelatin suspended in a balanced solution for the fluid resuscitation of patients with acute hypovolaemic shock?

CG174/5 | Training and education:- Does the introduction of hospital systems that ensure:
- all hospital healthcare professionals involved in prescribing and delivering IV fluid therapy are appropriately trained in the principles of fluid prescribing and
- all IV fluid therapy-related complications are reported lead to a reduction in IV fluid-related complications and associated healthcare costs?

CG175/1 | Prognostic indicators:- Further research is required into the identification of prognostic indicators in order to differentiate effectively between men who may die with prostate cancer and those who might die from prostate cancer. [2008]

CG175/3 | Using biomarkers to diagnose brain injury:- In adults with medium risk indications for brain injury under the 2014 NICE CT head injury guidance, what is the clinical and cost effectiveness of using the diagnostic circulating biomarker S100B to rule out significant intracranial injury?

CG175/5 | Duration of exercise to combat fatigue in men having androgen deprivation therapy:- Does a longer (more than 12 weeks) programme of supervised aerobic resistance exercise reduce fatigue more effectively than a 12-week programme in men having androgen deprivation therapy? Outcomes of interest are measures of fatigue, aerobic capacity, cardiovascular function and quality of life. [new 2014]

CG176/1 | Direct transport to a tertiary centre with neuroscience facilities versus transport to the nearest hospital:- Is the clinical outcome of patients with head injury with a reduced level of consciousness improved by direct transport from the scene of injury to a tertiary centre with neuroscience facilities compared with the outcome of those who are transported initially to the nearest hospital without neurosurgical facilities?

CG176/2 | Criteria for CT head scanning:- What is the clinical and cost effectiveness of the 2014 NICE guideline recommendation on CT head scanning versus clinical decision rules (including CHALICE, CATCH and PECARN) for selecting children and infants for head CT scanning?

CG176/3 | Antiplatelet and anticoagulant drugs:- In patients with head injury does the use of antiplatelet and anticoagulant drugs increase the risk of intracranial haemorrhage over and above factors included in the current recommendations for CT head scans?

CG176/4 | Using biomarkers to diagnose brain injury:- In adults with medium risk indications for brain injury under the 2014 NICE CT head injury guidance, what is the clinical and cost effectiveness of using the diagnostic circulating biomarker S100B to rule out significant intracranial injury?

CG176/5 | Predictors of long-term sequelae following head injury:- Research is needed to summarise and identify the optimal predictor variables for long-term sequelae following mild traumatic brain injury (TBI). A systematic review of the literature could be used to derive a clinical decision rule to identify relevant patients at the time of injury. This would in turn lay the foundation for a derivation cohort study.

CG177/1 | Treatments for osteoarthritis in very old people:- What are the short-term and long-term benefits of non-pharmacological and pharmacological treatments for osteoarthritis in very old people (for example, aged 80 years and older)?

CG177/2 | Combinations of treatments for osteoarthritis:- What are the benefits of combinations of treatments for osteoarthritis, and how can these be included in clinically useful, cost-effective algorithms for long-term care?

CG177/3 | Treating common presentations of osteoarthritis for which there is little evidence:- What are effective treatments for people with osteoarthritis who have common but poorly researched problems, such as pain in more than one joint or foot osteoarthritis?

CG177/4 | Biomechanical interventions in the management of osteoarthritis:- Which biomechanical interventions (such as footwear, insoles, braces and splints) are most beneficial in the management of osteoarthritis, and in which subgroups of people with osteoarthritis do they have the greatest benefit?

CG177/5 | Treatments that modify joint structure in people with osteoarthritis:- In people with osteoarthritis, are there treatments that can modify joint structure, resulting in delayed structural progression and improved outcomes?

CG178/2 | People who choose not to take antipsychotic medication:- What is the clinical and cost effectiveness of psychological intervention alone, compared with treatment as usual, in people with psychosis or schizophrenia who choose not to take antipsychotic medication?

CG178/3 | The physical health benefits of discontinuing antipsychotic medication:- What are the short- and long-term benefits to physical health of guided medication discontinuation and/or reduction in first episode psychosis and can this be achieved without major risks?

CG178/4 | Maintaining the benefits of early intervention in psychosis services after discharge:- How can the benefits of early intervention in psychosis services be maintained once service users are discharged after 3 years?

CG178/5 | Interventions for PTSD symptoms in people with psychosis and schizophrenia:- What is the benefit of a CBT-based trauma reprocessing intervention on PTSD symptoms in people with psychosis and schizophrenia?

CG179/5 | Repositioning:- When repositioning a person who is at risk of developing a pressure ulcer, what is the most effective position – and optimum frequency of repositioning – to prevent a pressure ulcer
developing?

CG180/1 | Cognitive behavioural therapy for people with atrial fibrillation:- What is the clinical and cost effectiveness of cognitive behavioural therapy (CBT) compared with usual care for people with newly diagnosed atrial fibrillation?

CG180/2 | Rate control drug treatment for people aged 75 and over with atrial fibrillation:- What is the comparative effectiveness of the 3 main drug classes used for rate control (beta-blockers, calcium-channel blockers and digoxin) in people aged 75 and over with atrial fibrillation in controlling symptoms, improving quality of life and reducing morbidity and mortality?

CG180/4 | Non-vitamin K antagonist oral anticoagulants:- Do people with atrial fibrillation whose anticoagulant control is poor, or is predicted to be poor, with warfarin benefit from changing to one of the non-vitamin K antagonist (non-VKA) oral anticoagulants?

CG181/1 | What is the effectiveness of age alone and other routinely available risk factors compared with the formal structured multifactorial risk assessment to identify people at high risk of developing CVD?

CG181/2 | What is the improvement in the cost-effectiveness metrics for statin therapy in reducing CVD that can be obtained when using a complete individual patient-based outcomes meta-analysis data set compared with using published outcomes data?

CG181/5 | What is the clinical effectiveness and rate of adverse events of statin therapy using atorvastatin 20 mg per day compared with atorvastatin 40 mg per day and atorvastatin 80 mg per day in people without established CVD?

CG182/1 | Does the provision of educational and supportive interventions to people with chronic kidney disease (CKD) by healthcare professionals increase patients' skills and confidence in managing their conditions and improve clinical outcomes?

CG182/2 | For people with CKD at the highest risk of cardiovascular disease, what is the clinical effectiveness of low-dose aspirin compared with placebo for primary prevention of cardiovascular disease?

CG183/1 | Designing systems for documenting drug allergy:- Which documentation strategies would be most clinically and cost effective to minimise the number of people who are re-exposed to drugs to which they have a suspected or confirmed allergy, looking in particular at:
- electronic health records that include features specifically designed to record and alert
clinicians to drug allergy information, compared with systems without such features and
- different formats for patient-held, structured drug allergy documentation?

CG183/2 | Communicating information about drug allergy:- In people with suspected or confirmed drug allergies, are patient-focused information strategies more effective than standard NHS practice in increasing people's likelihood of disclosing their drug allergy (or their suspected drug allergy) and therefore reducing the risk of being re-exposed to the affected drug?

CG183/3 | Using selective cyclooxygenase 2 inhibitors in people with previous severe allergic reactions to non-selective non-steroidal anti-inflammatory drugs:- Should all patients who have experienced a severe allergic reaction to a non-selective non-steroidal anti-inflammatory drug (NSAID) be assessed by specialist drug allergy services or should they be advised to take a selective cyclooxygenase 2 (COX 2) inhibitor without further investigations if clinically appropriate?

CG183/4 | Oral antibiotic challenge for diagnosing antibiotic allergy in children:- In children who have a suspected allergy to an antibiotic, is it clinically and cost effective to proceed directly (without prior skin or intradermal tests) to a diagnostic oral antibiotic challenge rather than referring them to specialist drug allergy services?

CG184/2 | Laparoscopic fundoplication compared with medical management:- What is the effectiveness of laparoscopic fundoplication compared with medical management in people with GORD that does not respond to optimal proton pump inhibitor (PPI) treatment?

CG184/4 | Other specialist management:- What specialist management is effective for people whose symptoms do not respond to PPIs despite optimum primary care, or for people whose symptoms return after surgery?

CG184/5 | Specialist investigation:- What specialist investigations should be conducted to exclude a diagnosis of functional dyspepsia in people with uninvestigated dyspepsia that does not respond to PPIs or H2 receptor antagonists (H2RAs) despite optimum primary care?

CG185/1 | Psychological interventions for young people with bipolar depression:- What is the clinical and cost effectiveness of structured psychological interventions for young people with bipolar depression?

CG185/2 | Maintenance treatment:- In the maintenance treatment of bipolar disorder, what is the relative effect on quality of life of lithium, an antipsychotic (haloperidol, olanzapine, quetiapine or risperidone), or a combination of lithium and an antipsychotic?

CG185/3 | Antidepressants combined with antimanic medication in bipolar depression:- What is the clinical and cost effectiveness of fluoxetine combined with olanzapine versus an alternative selective serotonin reuptake inhibitor (SSRI) combined with olanzapine in the treatment of moderate to severe bipolar depression?

CG185/4 | A specialised collaborative care service for people with bipolar disorder:- What is the clinical and cost effectiveness of a specialised collaborative care service for people admitted to hospital with bipolar disorder compared with usual treatment delivered by generic care services?

CG185/5 | Cognitive behavioural therapy for the long-term management of bipolar disorder:- What is the clinical and cost effectiveness of face-to-face cognitive behavioural therapy (CBT) compared with internet-facilitated CBT in the long-term management of bipolar disorder?

CG186/2 | Is intravenous methylprednisolone more clinically and cost effective than oral methylprednisolone in people with relapsing–remitting Multiple Sclerosis (MS) and people with secondary progressive MS with continued relapses?

CG187/1 | In people with acute heart failure, congestion and worsening renal function, does the addition of low-dose dopamine to standard therapy lead to greater diuresis and renal protection compared with adding placebo to standard therapy?

CG187/2 | In people with acute heart failure and persistent congestion, does the addition of a thiazide diuretic to standard therapy lead to greater diuresis compared with adding placebo to standard therapy?

CG187/4 | In people with decompensated heart failure, fluid congestion and diuretic resistance, does ultrafiltration lead to more rapid and effective decongestion compared with continuing diuretictreatment?

CG188/1 | What are the long-term benefits and harms, and cost effectiveness of endoscopic ultrasound (EUS) compared with magnetic resonance cholangiopancreatography (MRCP) in adults with suspected common bile duct stones?

CG188/3 | What models of service delivery enable intraoperative endoscopic retrograde cholangiopancreatography (ERCP) for bile duct clearance to be delivered within the NHS? What are the costs and benefits of different models of service delivery?

CG188/4 | In adults with common bile duct stones, should laparoscopic cholecystectomy be performed early (within 2 weeks of bile duct clearance), or should it be delayed (until 6 weeks after bile duct clearance)?

CG189/4 | What is the best way to deliver obesity management interventions to people with particular conditions associated with increased risk of obesity (such as people with a physical disability that limits mobility, a learning disability or enduring mental health difficulties)?

CG189/5 | What are the long-term effects of using very-low-calorie diets (VLCDs) versus low-calorie diets
(LCDs) on weight and quality of life in patients with a BMI of 40 kg/m2 or more, including the
impact on weight cycling?

CG190/3 | Does enhanced education specifically about the latent first stage of labour increase the number of nulliparous women who wait until they are in established labour before attending the obstetric or midwifery unit (or calling the midwife to a home birth), compared with women who do not receive this education?

CG190/5 | What are the natural frequencies of the avoidable harms that cardiotocography is intended to prevent for women who are assessed as being at low risk of complications at the start of labour? Does using cardiotocography in labours where complications develop confer a net benefit compared with intermittent auscultation?

CG191/2 | In patients hospitalised with moderate- to high-severity community-acquired pneumonia, does using C-reactive protein monitoring in addition to clinical observation to guide antibiotic duration safely reduce the total duration of antibiotic therapy compared with a fixed empirical antibiotic course?

CG191/3 | What is the clinical effectiveness of continuous positive pressure ventilation compared with usual care in patients with community-acquired pneumonia and type I respiratory failure without a history of chronic obstructive pulmonary disease?

CG28/1 | An appropriately blinded, randomised controlled trial should be conducted to assess the efficacy (including measures of family and social functioning as well as depression) and the cost effectiveness of another self-help intervention compared with computerised [Cognitive Behavioural Therapy (CBT)] and treatment as usual in a sample of children and young people treated in primary care who have been diagnosed with depression. The trial should be powered to examine the effect of treatment in children and young people separately and involve a follow-up of 12 to 18 months (but no less than 6 months).[2015]

CG28/2 | An appropriately blinded, randomised controlled trial should be conducted to assess the efficacy (including measures of family and social functioning as well as depression) and the cost effectiveness of individual [cognitive behavioural therapy] (CBT), systemic family therapy and child psychodynamic psychotherapy compared with each other and treatment as usual in a broadly based sample of children and young people diagnosed with moderate to severe depression (using minimal exclusion criteria). The trial should be powered to examine the effect of treatment in children and young people separately and involve a follow-up of 12 to 18 months (but no less than 6 months).[2015]

CG28/3 | An appropriately blinded, randomised controlled trial should be conducted to assess the efficacy (including measures of family and social functioning as well as depression) and the cost effectiveness of fluoxetine, the favoured psychological therapy [emerging from another suggested trial - as specified in paragraph 4.1 of the document], the combination of fluoxetine and psychological therapy compared with each other and placebo in a broadly based sample of children and young people diagnosed with moderate to severe depression (using minimal exclusion criteria). The trial should be powered to examine the effect of treatment in children and young people separately and involve a follow-up of 12 to 18 months (but no less than 6 months).[2015]

CG61/2 | Psychological interventions:- Are the psychological interventions [cognitive behavioural therapy] (CBT), hypnotherapy and psychological therapy all equally effective in the management of [Irritable bowel syndrome] (IBS) symptoms, either as first-line therapies in primary care, or in the treatment of people with IBS that is refractory to other treatments?

CG61/5 | Herbal medicines:- Are Chinese and non-Chinese herbal medicines safe and effective as first-line therapy in the treatment of [Irritable bowel syndrome] (IBS), and which is the most effective and safe option?

DG1/1 | Research is needed to quantify the health outcome benefits associated with imaging improvements with the EOS system. Examples of such benefits might include reduced back pain or reduced postural difficulties in people with scoliosis, or longer lasting and less painful joint replacements. Although research into the use of the EOS system is appropriate for all the indications included in the scope, the research most likely to be useful is for planning hip and knee replacement, including patient selection, device selection, and surgical approach. Joint replacement operations are more common than the other indications and the EOS system is thought to be most likely to provide benefit to these patients.

DG1/2 | Additional methodological research is needed to determine the most appropriate model structures to assess the benefit arising from radiation dose reduction. Additional work is needed to assess when the radiation-induced cancers actually occur and the impact of the timing of the emergence of cancer on health status.

DG10/1 | MammaPrint: research is recommended on the clinical validity of the test in people that are representative of the population in England. In particular, information on how the test reclassifies people when compared with current practice in England and their risk of distant recurrence would be useful. Research into the clinical utility of the test is also recommended; in particular, evidence of the impact of the test on clinical decision-making in England and robust data on its ability to predict the benefit of chemotherapy.

DG10/2 | Oncotype DX: research is recommended on the clinical utility of the test, including robust evidence on the impact of Oncotype DX on clinical decisionmaking in England (containing consideration of informal approaches compared with a formal algorithm for combining the Oncotype DX score with clinicopathological variables) and its ability to predict the benefit of chemotherapy. As part of the adoption of Oncotype DX by the NHS, NICE encourages the collection of clinical utility and any other useful data by the health system, potentially by a multicentre audit.

DG10/3 | IHC4: research into the analytical validity (reliability and reproducibility) of the complete IHC4 test is recommended (an algorithm combining 4 markers and classical clinical and pathological variables), particularly within the NHS and when performed in local laboratories. Studies to confirm the prognostic ability and to determine the impact of IHC4 on clinical decision-making in England and, ideally, to predict the benefit of chemotherapy are recommended.

DG10/4 | Mammostrat: research on the analytical validity (reliability and reproducibility) of the test is recommended. Research on the clinical utility of the test is also recommended. In particular, evidence of how the test reclassifies people's risk when compared with current practice in England, evidence on the impact of Mammostrat on clinical decision-making in England, and its ability to predict the benefit of chemotherapy.

DG11/1 | Further research is needed on the use and clinical utility of faecal calprotectin testing, and support pathways for the long-term management of these conditions in the community should be developed.

DG11/2 | Further research is needed on the impact of faecal calprotectin testing on clinical decision-making when added to current practice. This includes research into optimal cut-off values for tests and the investigation of repeat testing strategies in people with intermediate levels of faecal calprotectin. Development of a consistent definition for the 'intermediate range' is encouraged.

DG12/1 | NICE discussed the potential for future research. NICE accepted that there is a need to further establish the accuracy of current practice in diagnosing asthma and the incremental accuracy associated with
the addition of FeNO testing.

DG12/2 | NICE also considered the role of FeNO measurement in asthma management. It accepted that currently available evidence on the use of FeNO measurement in asthma management is unclear on whether benefits of treatment are maintained long-term. NICE concluded that long-term studies following patients for several years could address this gap.

DG12/3 | NICE also considered the role of FeNO in guiding inhaled corticosteroid dosing through stepping-up and stepping-down protocols. It accepted there is a need for more evidence on which protocols offer the safest and most optimal asthma management when used in UK clinical practice. Therefore, further studies are recommended, with consideration for the different protocols and cut-off points that may be necessary in different populations.

DG13/2 | NICE recommends further research in using viscoelastometric testing in the emergency control of bleeding after trauma and during postpartum haemorrhage to assess its effectiveness compared with standard laboratory testing. NICE recommends that outcomes should include, but may not be limited to, bleeding outcomes, mortality, duration of hospital or intensive care unit stay, transfusion rates and volumes transfused.

DG13/3 | NICE recommends further research comparing the clinical effectiveness of all 3 viscoelastometric devices (ROTEM, TEG and Sonoclot systems) in cardiac surgery and in the emergency control of bleeding after trauma and during postpartum haemorrhage. In particular, NICE recommends research to determine which of the parameters included in the viscoelastometric testing systems are the most significant in changing clinical decision-making and improving clinical outcomes. The degree of change needed in these parameters to affect clinical decision-making and clinical outcomes should also be considered.

DG13/4 | NICE recommends that future trials should include longer-term follow-up, beyond the initial hospital episode, with a view to informing the cost-effectiveness modelling and reducing uncertainty.

DG15/1 | NICE recommends that robust evidence be generated to show the clinical effectiveness of the AccuTnI+3 assay for the early rule out of non-ST-segment elevation myocardial infarction (NSTEMI) in people presenting to an emergency department with acute chest pain.Where possible the accuracy of the AccuTnI+3 assay and its resulting clinical outcomes should be compared with both high-sensitivity troponin assays recommended in section 1.1 of the guidance (DG15) and standard troponin assays.

DG15/2 | NICE recommends the collection of further outcome data through clinical audit in centres adopting 'early rule-out protocols' with high-sensitivity troponin testing. The data collected through audit should be sufficient to allow analysis of the optimal timing of samples taken after presentation to an emergency department and the optimal high-sensitivity troponin test cut-offs for both ruling out and ruling in NSTEMI.

DG15/3 | NICE recommends further research comparing the clinical effectiveness of different early rule-out test protocols using high-sensitivity assays which meet the criteria applied for this assessment. NICE recommends that future studies should include consideration of the clinical effectiveness of different test strategies including those employing low diagnostic thresholds, and the impact of different test strategies on both clinician behaviour and the health system, with a view to reducing uncertainty in the economic model. Future studies should also investigate the role of sex and age-specific 99th percentile thresholds in the assessment of suspected acute coronary syndrome. The Committee also considered that it would be appropriate to include adjudication with high-sensitivity troponin assays at time points earlier than 10–12 hours as the reference standard in future studies.

DG15/4 | NICE recommends further research to understand the underlying biological causes and the clinical implications of chronically elevated troponin levels in older people, and people with conditions known to cause troponin elevation in the absence of ischaemia.

DG16/1 | NICE recommends further research to validate the accuracy and precision of the My5-FU assay for the quantitative determination of 5-fluorouracil (5-FU) at the lower end of its measuring range with analytical reference standard methods, including high-performance liquid chromatography and liquid chromatography-mass spectrometry.

DG16/4 | NICE recommended further research to explore the impact of having experiences of patients having continuous infusion 5-FU and take into account the impact on quality of life. The potential consequences of introducing pharmacokinetic dose adjustment should also be explored.

DG5/1 | Research is recommended on the percentage of unenhanced ultrasound scans that are inconclusive, particularly in people with cirrhosis. Such studies should explicitly define and describe why scans are 'inconclusive'.

DG5/2 | Research is recommended on patient preferences, and their impact on quality of life, for contrast-enhanced ultrasound and other imaging modalities. Ideally such research should compare all appropriate imaging modalities in the same patient group.

DG7/1 | Research is needed to establish the validity and accuracy of the SeHCAT (tauroselcholic [75selenium] acid) test and of any potential alternative technologies for measuring bile acid malabsorption in people with chronic diarrhoea diagnosed with irritable bowel syndrome (IBS-D) or Crohn's disease without ileal resection.

DG7/2 | Research is needed to establish the nature of bile acid malabsorption and whether bile acid malabsorption is a primary or secondary condition in people diagnosed with irritable bowel syndrome (IBS-D) or Crohn's disease without ileal resection.

DG8/1 | NICE recommends that a national registry is developed to collect data on the use of the RD-100i OSNA system in detecting sentinel lymph node metastases during breast cancer surgery. It also recommends that data on all patients having whole lymph node analysis by the RD-100i OSNA system should be submitted to this registry. These data should be integrated with data from other registries for breast cancer where appropriate.

HST1/1 | NICE recommends the use of eculizumab for atypical haemolytic uraemic syndrome (aHUS) only if all the following arrangements are in place:
- coordination of eculizumab use through an expert centre
- monitoring systems to record the number of people with a diagnosis of atypical
- haemolytic uraemic syndrome and the number who have eculizumab, and the dose and duration of treatment
- a national protocol for starting and stopping eculizumab for clinical reasons
- a research programme with robust methods to evaluate when stopping treatment or dose adjustment might occur.

HST1/2 | There is a need for further evidence on the long-term outcomes of treatment with eculizumab, and on the effect of treatment in children, adolescents and during pregnancy. The Committee supports enrolment of patients into the aHUS registry and the collection of high-quality information from these registries periodically to inform treatment decisions.

IPG375/1 | Current evidence on the efficacy and safety of distal iliotibial band lengthening for refractory greater trochanteric pain syndrome is inadequate in quantity and quality. Therefore this procedure should only be used in the context of research. Research studies should clearly define patient selection, and outcomes should include measures of function and quality of life.

IPG376/1 | NICE encourages further research into extracorporeal shockwave therapy (ESWT) for refractory greater trochanteric pain syndrome. Research studies should clearly describe patient selection, imaging, and treatment protocols. Outcomes should include functional and quality-of-life scores with at least 1 year of follow-up.

IPG380/1 | Further research into percutaneous atherectomy of femoropopliteal arterial lesions with plaque excision devices should take the form of well-conducted trials, which should define patient selection, treatment protocols and location and types of arterial lesions treated, and report long-term patency outcomes. NICE may review this procedure on publication of further evidence.

IPG381/1 | Further research studies into deep brain stimulation (DBS) for intractable trigeminal autonomic cephalalgias (TACs) should clearly define patient selection and report the intensity and duration of stimulation, medication use and quality of life, in addition to documenting the effects on headache symptoms as clearly as possible.

IPG383/1 | Further research into hand allotransplantation should include data on long-term functional outcomes, and any occurrence of malignancy associated with long-term immunosuppression should be published. NICE may review this procedure on publication of further evidence.

IPG387/1 | NICE encourages further research into transaxial interbody lumbosacral fusion. Research outcomes should include fusion rates, pain and functional scores, quality of life measures and the frequency of both early and late complications. NICE may review this procedure on publication of further evidence.

IPG391/1 | NICE encourages further research into the use of innovative technologies for the management of severe acute respiratory failure, and may review this guidance on publication of further evidence.

IPG393/1 | Further research into endoscopic radiofrequency therapy of the anal sphincter for faecal incontinence should clearly define the patient groups being treated. It should also report the clinical impact in terms of quality of life and long-term outcomes. NICE may review the procedure on publication of further evidence.

IPG394/1 | Further research on external aortic root support in Marfan syndrome should report on long-term outcomes, particularly the occurrence of dissection and aortic dilatation, and the need for further procedures.

IPG401/1 | Safety of selective internal radiation therapy (SIRT) is a potentially beneficial treatment for patients with on-resectable colorectal metastases in the liver, but that more research and data collection are required to demonstrate its efficacy.

IPG402/1 | Collection and publication of data on the outcomes of percutaneous cryotherapy for renal cancer in the long term is encouraged. Further research should compare the long-term outcomes of cryotherapy with those of other treatments for renal cancer.

IPG406/1 | NICE encourages further research into microwave ablation for the treatment of liver metastases. Research should clearly define patient selection criteria and report tumour recurrence and patient survival. Comparison with other ablative techniques would be useful. NICE may review the procedure on publication of further evidence.

IPG409/1 | Balloon dilatation of the Eustachian tube should only be used in the context of research, which should address the efficacy of the procedure in the short and longer term, and also document safety outcomes. Research studies should clearly describe which parts of the Eustachian tube are being treated and report subjective measurements of symptom improvement and objective measurements of Eustachian tube function.

IPG412/1 | Drainage, irrigation and fibrinolytic therapy (DRIFT) for post-haemorrhagic hydrocephalus in preterm infants should only be used in the context of research. Research should aim to establish the risk of secondary haemorrhage and its consequences, and the need for shunt insertion. Outcomes should include death and disability in the long-term: these should be reported separately.

IPG413/1 | NICE encourages further research into the efficacy of MRI-guided transcutaneous focused ultrasound for uterine fibroids. Research studies should report long-term outcomes, including the need for further treatment. Data on the incidence and outcomes of subsequent pregnancy in patients who choose this procedure because they wish to maintain or improve their fertility are particularly important.

IPG415/1 | Epiretinal brachytherapy for wet age-related macular degeneration (AMD) should only be used in the context of research. Research studies should address whether epiretinal brachytherapy reduces the progression of wet AMD and whether it can reduce the number of injections of antivascular endothelial growth factor agents (anti-VEGF) required. Long-term outcomes should be reported.

IPG416/1 | Further research on the efficacy of deep brain stimulation (DBS) for refractory epilepsy should describe patient selection and define clearly the target area of the brain. Outcomes should include measures of seizure frequency, functional ability, social inclusion and quality of life.

IPG418/1 | NICE encourages further research on percutaneous transluminal radiofrequency sympathetic denervation of the renal artery for resistant hypertension. Patient selection criteria should be described clearly and reported outcome measures should include adverse events and the long-term effect of the procedure on blood pressure.

IPG418/2 | NICE also encourages data collection and publication of outcomes on all patients having percutaneous transluminal radiofrequency sympathetic denervation of the renal artery for resistant hypertension. Clinicians should submit data on all patients having this procedure to the national register when it becomes available.

IPG419/1 | NICE encourages further research into bronchial thermoplasty for severe asthma. Research outcomes should include objective measurements of lung function, symptom control, medication requirements and quality of life. Long-term safety and efficacy outcomes are particularly important. Collaboration between units to publish data on patients not involved in research studies would also be valuable.

IPG420/1 | NICE encourages further research on percutaneous venoplasty for chronic cerebrospinal venous insufficiency (CCSVI) for multiple sclerosis (MS), in the form of robust controlled clinical trials. Studies should clearly define selection criteria and patient characteristics. They should also clearly define technical success which may include measurement of pressure gradients across treated vein segments before and after venoplasty. Outcomes should include clinical and quality of life measures.

IPG421/1 | NICE encourages further research into transcatheter aortic valve implantation (TAVI) for aortic stenosis. In particular, NICE encourages clinicians to enter all suitable patients into the UK TAVI trial. Information from research trials that will be useful for future guidance includes patient selection criteria and comparisons between TAVI and surgical aortic valve replacement (SAVR) in patients who would be suitable for either procedure. Outcomes should include incidence of stroke and other adverse events, symptom relief, quality of life, occurrence of aortic regurgitation, and valve durability in the short and long term.

IPG422/1 | Further research on incisionless otoplasty should describe the precise surgical techniques used and should report both short- and long-term outcomes, including the need for further procedures.

IPG423/1 | NICE encourages further research into focal cryoablation for localised prostate cancer. This should take the form of controlled studies comparing the procedure against other forms of management. Studies should clearly define patient selection criteria and should report outcomes including local recurrence in the long term.

IPG423/2 | Clinicians should collect data on all patients undergoing focal cryoablation (including details of case selection, methods of follow-up and outcomes) for local audit. Clinicians should enter details about all patients undergoing focal therapy using cryoablation for localised prostate cancer onto the European Registry for Cryosurgical Ablation of the Prostate (EuCAP) register and review clinical outcomes locally.

IPG424/1 | NICE encourages further research into focal therapy using high-intensity focused ultrasound (HIFU) for localised prostate cancer. This should take the form of controlled studies comparing the procedure against other forms of management. Studies should clearly define patient selection criteria and should report outcomes including local recurrence in the long term.

IPG424/2 | Clinicians should collect data on all patients undergoing focal high-intensity focused ultrasound (HIFU) (including details of case selection, methods of follow-up and outcomes) for local audit and for submission to national and/or international registers when these become available. The European Registry for Cryosurgical Ablation of the Prostate (EuCAP) register is being developed to receive data on focal therapy using HIFU for localised prostate cancer. When this facility is available clinicians should submit data on all patients undergoing focal therapy using HIFU for localised prostate cancer to that register.

IPG425/1 | Further information from research and collaborative data collection would be useful. This should include clearly defined patient selection criteria and long-term outcomes. NICE may review this procedure on publication of further evidence.

IPG426/1 | NICE encourages further research into micropressure therapy for refractory Ménière's disease. Research studies should report long-term outcomes, in particular the need for subsequent surgical treatment.

IPG427/1 | NICE encourages clinicians to enter patients into research studies with the particular aims of guiding selection of patients and of defining the place of percutaneous balloon cryoablation in relation to other procedures for treating atrial fibrillation. Further research should define patient selection criteria clearly and should document adverse events and long-term control of atrial fibrillation.

IPG429/1 | Endovascular stent insertion for intracranial atherosclerotic disease should only be used in the context of research. Research should clearly define patient selection and be designed to provide outcome data based on follow-up of at least 2 years.

IPG430/1 | NICE encourages further research and data collection on partial replacement of the meniscus of the knee using a biodegradable scaffold. This should include clear descriptions of patient selection and adjunctive treatments. Outcome measures should include symptom relief and functional ability in the short term and the need for further treatment in the longer term.

IPG431/1 | NICE encourages further research and collaborative data collection on laparoscopic insertion of a magnetic bead band for gastro-oesophageal reflux disease (GORD). Clear descriptions of patient selection are particularly important. Perioperative and long-term complications should be reported, together with details of long-term efficacy, including the need for further procedures and medication to control symptoms of GORD. NICE may review the procedure on publication of further evidence.

IPG432/1 | NICE encourages further research on laparoscopic gastric plication for severe obesity, which should include information about long-term efficacy and safety, and specifically how the procedure influences further gastric surgery. Comparison with alternative procedures would be useful.

IPG434/1 | NICE encourages further research and data collection on radiofrequency cold ablation for respiratory papillomatosis. In particular, research and data collection should report treatment indication (whether for primary or secondary treatment of respiratory papillomatosis), outcomes related to timing and site of disease recurrence, the need for tracheostomy after the procedure, and longer-term survival. In addition, any effect of the procedure on voice quality should be documented.

IPG437/1 | NICE encourages further research comparing autologous blood injection (with or without techniques to produce platelet-rich plasma) against established treatments for managing plantar fasciitis. Trials should clearly describe patient selection, including duration of symptoms and any prior treatments. Outcomes should include specific measures of pain and function.

IPG438/1 | NICE encourages further research comparing autologous blood injections (with or without techniques to produce platelet-rich plasma) against established nonsurgical methods for managing tendinopathy. Trials should clearly describe patient selection (including the site of tendinopathy, duration of symptoms and any prior treatments) and document whether a 'dry needling' technique is used. Outcomes should include specific measures of pain, quality of life and function, and whether subsequent surgical intervention is needed.

IPG439/1 | Further research and publication of observational data would be useful. Publications should describe details of patient selection, particularly in relation to previous treatments. They should also describe clinical outcomes (including all complications) and patient experience in the longer term. NICE may review the procedure on publication of further evidence.

IPG441/1 | Current evidence on the safety and efficacy of irreversible electroporation for treating primary lung cancer and metastases in the lung is inadequate in quantity and quality. Therefore, this procedure should only be used in the context of research. In particular, studies should report the effect of the procedure on local tumour control and patient survival.

IPG442/1 | Current evidence on the safety and efficacy of irreversible electroporation for treating pancreatic cancer is inadequate in quantity and quality. Therefore, this procedure should only be used in the context of research. In particular, studies should report the effect of the procedure on local tumour control and patient survival.

IPG443/1 | Current evidence on the safety and efficacy of irreversible electroporation for treating renal cancer is inadequate in quantity and quality. Therefore, this procedure should only be used in the context of research. In particular, studies should report the effect of the procedure on local tumour control and patient survival.

IPG444/1 | Current evidence on the safety and efficacy of irreversible electroporation for treating primary liver cancer is inadequate in quantity and quality. Therefore, this procedure should only be used in the context of research. In particular, studies should report the effect of the procedure on local tumour control and patient survival.

IPG445/1 | Current evidence on the safety and efficacy of irreversible electroporation for treating liver metastases is inadequate in quantity and quality. Therefore, this procedure should only be used in the context of research. In particular, studies should report the effect of the procedure on local tumour control and patient survival.

IPG450/1 | NICE encourages further research into percutaneous electrical nerve stimulation (PENS) for refractory neuropathic pain, particularly to provide more information about selection criteria and long-term
outcomes, with clear documentation of the indications for treatment.

IPG453/1 | Further research on prostate artery embolisation for benign prostatic hyperplasiain the form of randomised trials or cohort studies (for example, using an appropriate register) should clearly document patient selection criteria and all complications, specifically including disturbance of sexual function. Efficacy outcomes should include measures of urinary function, symptoms and quality of life. Information about longer-term outcomes, including the need for further treatment, would be valuable.

IPG456/1 | NICE encourages further research into sutureless aortic valve replacement for aortic stenosis. Studies should document patient selection, aortic cross-clamp times, cardiopulmonary bypass times, perioperative morbidity and specifically the incidence of paravalvular (and central) leaks in the short and long term. Research comparing outcomes of the procedure against those of standard surgical aortic valve replacement would be useful.

IPG458/1 | Patients with acute ischaemic stroke for whom thrombolysis is unsuitable or has failed: Submit details of all patients to the Safe Implementation of Treatments in Stroke Thrombectomy (SITS-TBY) register. NICE encourages prospective studies of mechanical clot retrieval in these patients, including comparison of outcomes against those of patients who do not have the procedure. These studies should report details of patient selection, timing of the intervention after onset of symptoms, the devices and techniques used, and functional outcomes.

IPG458/2 | Patients with acute ischaemic stroke for whom thrombolysis is suitable: The procedure should only be used in the context of research:
- Research should include randomised studies comparing mechanical clot retrieval against thrombolysis or other current methods of management and should report details of patient selection, timing of the intervention after onset of symptoms, the devices and techniques used, complications and functional outcomes.
- NICE encourages clinicians to enter patients into randomised trials such as the PISTE trial. In addition, details of all patients should be entered into the SITS-TBY register.

IPG459/1 | NICE encourages research to guide future use of selective internal radiation therapy (SIRT) for primary intrahepatic cholangiocarcinoma. This should document patient characteristics, tumour response, survival and quality of life measures, and details of other treatments used adjunctively or sequentially. NICE may review the procedure on publication of further evidence.

IPG463/1 | NICE encourages further research into the insertion and use of implantable pulmonary artery pressure monitors in chronic heart failure, particularly studies that look at their long-term effects on hospital admissions and quality of life and that record adverse events.

IPG464/1 | Further research, in the form of comparative or observational studies, should document details of patient selection and should report all adverse events. Outcomes should include survival, quality of life, biliary patency and the need for further procedures.

IPG465/1 | NICE encourages further research into insertion of endobronchial valves for lung volume reduction in emphysema. Research should take the form of studies that allow comparison of the procedure with the natural history of the disease and other treatment options including surgery. The studies should define the criteria and techniques used for patient selection. Outcome measures should include lung function, dyspnoea score, exercise tolerance, quality of life and long-term safety.

IPG466/1 | NICE encourages further research into CXL using riboflavin and UVA for keratoconus and keratectasia, especially epithelium-on (transepithelial) CXL and the combination (CXL-plus) procedures. Details of the techniques used should be clearly described. Reported outcomes should include visual acuity, corneal topography and quality of life. Data on long-term outcomes for all types of CXL using riboflavin and UVA for keratoconus and keratectasia would be useful – specifically data about prevention of progression to corneal transplantation and about repeat procedures and their efficacy.

IPG467/1 | NICE encourages further research into the role of negative pressure wound therapy (NPWT) for the open abdomen. Patient selection should be documented and research should report on efficacy outcomes such as impact on wound care and healing rates, and duration of hospital stay.

IPG469/1 | NICE encourages further research into microwave ablation for treating primary lung cancer and metastases in the lung. Research studies should report details of patient selection and adverse events. Outcomes should include local tumour control, survival and quality of life.

IPG470/1 | NICE encourages further research on ultra-radical (extensive) surgery for advanced ovarian cancer, either in the form of research trials or in audits intended for publication (ideally by collaboration between units). Clinicians should ensure that details of patient selection and the precise extent of surgery are fully documented. Reported outcomes should include all complications, survival, and quality of life. Trials comparing complication rates, survival and quality of life against those of standard surgery and chemotherapy would be especially useful.

IPG471/1 | Well-controlled studies are needed to support the current limited evidence on weight loss in the short term. They should document patient selection, all complications (while the device is in place and after its removal) and technical problems associated with placing and removing the device.

IPG473/1 | NICE encourages further research into the effects of uterine artery embolisation compared with other procedures to treat adenomyosis, particularly for patients wishing to maintain or improve their fertility.

IPG474/1 | NICE encourages further research into arthroscopic trochleoplasty for patellar instability, including publication of consecutive patient series. Patient selection should be described in detail. Reported outcomes should include functional and quality‑of‑life measures, as well as reoperation rates.

IPG475/1 | NICE encourages further research and publication of results from consecutive case series of patients having this procedure. Details of patient selection should be clearly documented. Reported outcomes should include the effects of the procedure on symptoms and quality of life, the duration of benefits, and the need for further procedures. All complications should be reported. NICE may review this procedure in the light of longer-term outcomes.

IPG476/1 | NICE encourages further research into radiofrequency ablation of the soft palate for snoring. This could take the form of data collection, with the specific aim of documenting long-term outcomes and the need for further treatment.

IPG477/1 | NICE encourages further research on transcranial magnetic stimulation (TMS) for treating and preventing migraine. Data should be collected for all patients not entered into controlled trials. Studies should describe clearly whether its use is for treatment or prevention. They should report details of patient selection and the dose and frequency of use. Outcome measures should include the number and severity of migraine episodes, and quality of life in both the short and long term. The development of any neurological disorders (such as epilepsy) in the short or longer term after starting treatment should be documented.

IPG479/1 | Research (which may include observational studies) should clearly document the indications for use of the procedure and details of patient selection. Reported outcomes should include quality of life, overall survival and paracentesis-free survival, duration of function of the drainage system, nutritional parameters and any complications associated with its implantation or use.

IPG480/1 | Further research into endoscopic thoracic sympathectomy (ETS) for primary facial blushing should include clear information on patient selection and should seek to identify which patient characteristics might predict severe side effects. All complications should be reported. Outcomes should include measurements of efficacy, including quality of life and social functioning both in the short and long term, and in particular the frequency and severity of compensatory hyperhidrosis.

IPG481/1 | NICE encourages further research into optical coherence tomography (OCT) to guide PCI compared against percutaneous coronary intervention (PCI) with no intravascular imaging or PCI with intravascular ultrasound. Research outcomes should include data on medium- and long-term clinical outcomes, including the need for revascularisation.

IPG482/1 | NICE encourages further research into efficacy of extracorporeal membrane oxygenation (ECMO) for acute heart failure. This should include clear documentation of patient selection and indications for the use of ECMO. Outcome measures should include survival, quality of life and neurological status.

IPG486/1 | NICE encourages further research into hysteroscopic morcellation of uterine fibroids. Patient selection should be clearly described. Outcomes should include symptom relief, quality of life, recurrence rates and information about fertility and subsequent pregnancies. All complications should be documented.

IPG487/1 | Further research into efficacy and safety of endoscopic thoracic sympathectomy (ETS) for primary hyperhidrosis of the upper limb should include clear information on patient selection and should seek to identify which patient characteristics might predict severe side effects. All complications should be reported. Outcomes should include measurements of efficacy, including quality of life and social functioning both in the short and long term and in particular the frequency and severity of compensatory hyperhidrosis.

IPG488/1 | Chemosaturation via percutaneous hepatic artery perfusion and hepatic vein isolation for primary or metastatic liver cancer ('hepatic chemosaturation') should only be performed within the context of research, which may take the form of observational studies.

IPG490/1 | NICE encourages further research into transcutaneous neuromuscular electrical stimulation (NMES) for oropharyngeal dysphagia, which should clearly document the indications for treatment and the details of patient selection. Research should document the timing of initiation of treatment after onset of symptoms, as well as precise information about the procedure technique. Outcome measures should include freedom from tube feeding, quality of life and duration of treatment effect. NICE may review the procedure on publication of further evidence.

IPG491/1 | Further research into platelet-rich plasma injections for treating osteoarthritis of the knee should clearly describe patient selection and should take the form of well-designed, controlled studies that compare the procedure against other methods of management. Outcomes should include measures of knee function, patient-reported outcome measures and the timing of subsequent interventions. Studies aimed at assessing possible cartilage repair after platelet-rich plasma injections should include detailed radiographic or MRI imaging before and after the procedure.

IPG492/1 | NICE encourages further research into bioresorbable stent implantation for treating coronary artery disease and may review the procedure on publication of further evidence. Details of subsequent antiplatelet therapy should be reported and outcomes should include major adverse cardiac events (MACE) and target vessel revascularisation (defined as any repeat percutaneous intervention or surgical bypass of any segment of the treated vessel), particularly in the long term (at least 2–3 years). Studies on the safety and efficacy of the procedure compared with other types of coronary stent implantation would be useful.

IPG493/1 | Further research into arthroscopic radiofrequency chondroplasty of the knee should clearly document patient selection and the types of chondral defects being treated. More evidence on long-term outcomes would be useful.

IPG496/1 | NICE encourages further research into endoscopic radiofrequency ablation for Barrett's oesophagus with no dysplasia. Studies should define clearly the policies used for histological diagnosis. Outcomes should include complete resolution of Barrett's oesophagus, change and progression to low-grade dysplasia, high-grade dysplasia or cancer. All complications should be reported, particularly development of strictures. Comparative studies against surveillance would be useful.

IPG497/1 | NICE encourages further research into endoscopic radiofrequency ablation for squamous dysplasia of the oesophagus, including observational data collection. Studies should clearly define patient selection. Outcomes should include completeness of ablation, resolution of squamous dysplasia, progression to cancer and quality of life. All complications should be reported, particularly development of oesophageal strictures.

IPG502/1 | NICE encourages further research into the use of a wireless capsule to assess motility of the gastrointestinal tract. Studies should include clear details of patient selection. They should report on the diagnostic accuracy of the procedure in different parts of the gastrointestinal tract, and should provide data on the clinical benefits of the procedure for patients.

IPG504/1 | NICE encourages further research into valve-in-valve transcatheter aortic valve implantation (ViV-TAVI) for aortic bioprosthetic dysfunction. Comparative studies between ViV-TAVI and surgical aortic valve replacement (SAVR) for patients who are judged to have a low risk from SAVR should describe patient selection clearly and should report fully on complications and valve durability in the short and long term.

IPG505/1 | Further research should focus on the extended use of telemetric adjustable pulmonary artery banding for ventricular retraining and for its use pending the resolution of ventricular septal defects. Data collection may provide useful information. NICE may review the procedure on publication of further evidence.

IPG506/1 | NICE encourages further research on insertion of an annular disc implant at lumbar discectomy, particularly comparative trials. All studies should report details of patient selection and recurrence rates.

IPG507/1 | NICE encourages further research into insertion of a collagen plug to close an abdominal wall enterocutaneous fistula. Research should ideally take the formof prospective studies that compare the course of the enterocutaneous fistula (its natural history) with and without use of the procedure. Reports should record the conditions underlying all fistulas that are treated, their location, whether they are high or low output, and details of previous treatments. NICE may update the guidance on publication of further evidence.

IPG509/1 | Further research should include clear documentation of patient selection and of all complications. Outcomes should include pregnancy rates, live birth rates and instances of preterm delivery. Comparative studies would be helpful. NICE may update the guidance on publication of further evidence.

IPG511/1 | Further research into open reduction of slipped capital femoral epiphysis should clearly describe details of clinical presentation (for example, Loder classification), the degree of slip, its stability, and the surgical technique used; including whether surgical dislocation of the hip was done. Outcomes from 2 years onwards should include degree of correction, occurrence of avascular necrosis and need for subsequent hip surgery (and its timing).

IPG512/1 | Further research into implantation of a shock or load absorber for mild to moderate symptomatic medial knee osteoarthritis should include comparative studies against existing forms of management. Studies should record patient selection, functional outcomes, quality of life and complications. They should also report the nature and timing of any further surgery on the knee and the effect of removing the device. A minimum follow-up period of 2–3 years is needed. NICE may update the guidance on publication of further evidence.

IPG514/1 | NICE encourages further research into transanal total mesorectal excision (TaTME) of the rectum. Patient selection should be explicitly documented. If the procedure is used to treat malignancy, outcomes should include completeness of excision, recurrence rates, survival, quality of life outcomes and avoidance of the need for a stoma in the long term. All complications should be reported, specifically including incontinence.

IPG515/1 | Further research and data collection for inserting a balloon device to disimpact an engaged fetal head before an emergency caesarean section should report the impact of performing the procedure on the time taken from the decision to perform a caesarean section to delivery of the baby. Technical failures, including the need for repositioning of the device and for subsequent manual disimpaction of the fetal head; and any complications resulting from use of the procedure should be recorded. Fetal outcomes should also be reported. NICE may update the guidance on publication of further evidence.

IPG517/1 | Current evidence on the safety and efficacy of the insertion of endobronchial nitinol coils to improve lung function in emphysema is limited in quantity and quality. Therefore the procedure should only be used in the context of research.

IPG518/1 | Current evidence on the safety and efficacy of implantation of a duodenal–jejunal bypass liner for managing type 2 diabetes is limited in quality and quantity. Therefore the procedure should only be used in the context of research.

MTG19/1 | NICE considered that further research on the geko device in clinical settings could focus on reducing the current uncertainties about the reduction in relative risk in the defined patient population, and allow investigation into its use in broader patient populations.

MTG20/1 | Research is recommended to address uncertainties about the claimed patient and system benefits of using Parafricta Bootees and Undergarments. This should take the form of comparative research against standard care, preferably carried out in a hospital.

MTG21/1 | Research is recommended to address uncertainties about the claimed patient and system benefits of the ReCell Spray-On Skin system. Clinical outcomes should include time to 95% healing, length of hospital stay, cosmetic appearance of the scar and function of the burned area, compared with standard care.

MTG22/1 | Research is recommended to address uncertainties in the potential benefits to patients and the NHS of using VibraTip. Research is needed into the diagnostic accuracy of VibraTip compared with the 10 g monofilament and calibrated tuning fork in the diagnosis of peripheral neuropathy in people with diabetes. This research should also address the assessment of vibration perception compared with touch sensation in this clinical context.

MTG3/1 | NICE considered that further research would be helpful to compare the CardioQ-ODM with other techniques for monitoring cardiac output, particularly in patients in the critical care environment.

MTG4/1 | Research is recommended in the UK clinical setting to compare the BRAHMS copeptin assay in combination with cardiac troponin testing against sequential cardiac troponin testing for ruling out myocardial infarction.

MTG5/1 | Comparative research is recommended in the UK to reduce uncertainty about the outcomes of patients with chronic, ‘hard-to-heal’, complex wounds treated by the MIST Therapy system compared with those treated by standard methods of wound care. This research should define the types and chronicity of wounds being treated and the details of other treatments being used. It should report healing rates, durations of treatment (including debridement) needed to achieve healing, and quality of life measures (including quality of life if wounds heal only partially). It is recommended that centres using the MIST Therapy system take part in research that delivers these outcomes. Current users of the MIST Therapy system who are unable to join research studies should use NICE’s audit criteria to collect further information on healing rates, duration of treatment and quality of life and publish their results.

NG2/2 | Is primary radical cystectomy more effective than primary intravesical BCG (Bacille Calmette-Guérin) in high risk non-muscle-invasive bladder cancer, in terms of quality of life and cancer-specific outcomes?

NG2/4 | In patients with muscle-invasive bladder cancer suitable for radical treatment, does the use of
biomarkers enable patients to select more effective treatment, and improve their outcomes,
compared with treatment selected without biomarkers?

NG2/5 | Is symptom-based review as effective as scheduled follow-up for people treated with radical
cystectomy or radical radiotherapy for organ-confined, muscle-invasive bladder cancer? Outcomes
of interest are overall survival, health-related quality of life, resource use and cost.

NG3/5 | Are there effective long-term pharmacological interventions to prevent the onset of type 2
diabetes that can be recommended postnatally for women who have been diagnosed with
gestational diabetes?

NG4/1 | What is the relationship between midwifery staffing and outcomes in maternity settings in
England, and what factors act as modifiers or confounders of the relationship between midwifery
staffing and outcomes?

NG4/2 | What is the effectiveness of Birthrate Plus compared with other decision support methods or
professional judgement for identifying safe midwifery staffing requirements and midwifery skill
mix for maternity services in England?

NG5/1 | Is a medication review more clinically and cost effective at reducing the suboptimal use of medicines and medicines-related patient safety incidents, compared with usual care or other
interventions, in children?

NG5/2 | Is a medication review more clinically and cost effective at reducing the suboptimal use of
medicines and improving patient-reported outcomes, compared with usual care or other
intervention in the UK setting?

NG5/3 | What is the clinical and cost effectiveness of using clinical decision support systems to reduce the
suboptimal use of medicines and improve patient outcomes from medicines, compared with usual
care, in the UK setting?

NG5/4 | What models of cross-organisational working improve clinical and cost effectiveness in relation to
the suboptimal prescribing of medicines – for example, between NHS and social care, or primary
and secondary care, or between NHS and commercial organisations?

NG6/2 | What are the barriers to, and facilitators for, action and coping strategies among people vulnerable to cold-related illness and death with respect to cold homes (including ventilation)? (This includes self-disconnection when using pre-payment meters.)

NG6/4 | What is the relationship between improved home energy efficiency and the indoor temperature selected by people living in a representative cohort of UK housing types? What is the trade-off between reduced fuel bills and higher indoor temperatures following alterations to home energy efficiency?

NG6/5 | What opportunities are there to use electronic systems to reduce the health risks associated with cold homes? For example, could temperature alert systems be linked from a smart meter to a health or social care provider?

PH32/1 | What is the incidence and prevalence of, and what are the demographic trends in, skin cancer in the UK? (Demographic variables might include whether someone is an outdoor or indoor worker, their skin type and socioeconomic status.)

PH32/2 | What types of information provision, including mass-media campaigns, are effective and cost effective in preventing skin cancer in the UK? What factors influence effectiveness and cost effectiveness?
•Does effectiveness and cost effectiveness vary for different population groups? (Groups could be defined by gender, age, race/ethnicity, socioeconomic status or other characteristics such as lifestyle and at-risk behaviours.)
• What impact do they have on knowledge, attitudes, awareness and behaviour, including any impact on physical activity levels and vitamin D-related outcomes?
• What are the key factors that aid or hinder the success of these interventions or campaigns, including for different population groups? In particular, how does changing attitudes to sunbathing and tanning – and perceptions of the risk of skin cancer –influence success? Do attitudes vary for different population groups?

PH32/3 | Which new (previously not researched) primary prevention interventions (that do not include information provision as a component) are effective and cost effective in preventing skin cancer in the UK? What factors influence effectiveness and cost effectiveness?

PH33/1 | What HIV testing services (both health and non-healthcare based) are effective and cost effective in increasing the uptake of HIV testing among black African communities living in England? (Examples may include tests in the home, within genitourinary medicine [GUM] clinics or in community venues.) Does effectiveness and cost effectiveness vary for different population groups? (Groups could be defined by gender, age, race/ethnicity, sexuality, faith, socioeconomic status or other characteristics such as lifestyle, those living in high or low HIV prevalence areas, those who have previously tested or not tested or at risk behaviours).

PH33/2 | What factors aid or hinder the provision or uptake of HIV testing services in health and non-healthcare settings from the perspective of black African communities and different service providers (for example, healthcare professionals)? What ways of working or interventions can help overcome or make use of these factors?

PH33/3 | How does HIV testing affect the subsequent sexual behaviour of black Africans living in England? How does this differ by the test result and population factors such as gender, age, sexuality, faith, culture? Does normalising HIV testing help change knowledge, attitudes and behaviour among black Africans living in England?

PH33/4 | What interventions provide an effective and cost effective way of changing risky sexual behaviour after an HIV test (positive or negative) among black African communities living in England? What mechanisms lead to change and what, in particular, is effective and cost effective with higher risk sub-groups?

PH33/5 | Are antenatal settings an effective and cost- effective location for increasing the uptake of HIV testing for black African male partners of women attending antenatal appointments? What factors influence the suitability and acceptability of antenatal settings; for example does acceptability vary by clinic setting (such as community or hospital based); by population factors (such as age, faith, race/ethnicity, or socioeconomic status) or by other characteristics such as lifestyle, those living in high or low HIV prevalence areas, whether or not they have had a previous test or whether they are involved in risky behaviours)?

PH34/1 | What interventions provide an effective and cost effective way of increasing awareness and uptake of HIV testing among men who have sex with men (at population, community and individual level)? How does HIV testing affect the subsequent sexual behaviour of men who have sex with men? How does this differ by the test result and population factors such as gender, age, sexuality, faith and culture?

PH34/2 | What interventions provide an effective and cost effective way of changing risky sexual behaviour after an HIV test (positive or negative)? What mechanisms lead to change and what, in particular, is effective with higher risk sub-groups?

PH35/1 | How effective and cost effective are interventions which use either a ‘total population’ or ‘high-risk population’ approach to preventing type 2 diabetes among people from black and minority ethnic or lower socioeconomic groups?

PH35/2 | What are the most effective and cost effective ways of developing, implementing and assessing tailored and culturally appropriate community-level interventions to prevent type 2 diabetes among people at high risk? This includes people from a range of black and minority ethnic groups and those from lower socioeconomic communities.

PH35/3 | Which participatory approaches are most effective and cost effective among populations at higher risk of type 2 diabetes? This should consider the awareness, knowledge, understanding and skills of the providers of interventions for people at high risk of developing type 2 diabetes?

PH35/4 | How do socioeconomic, environmental, biological and psychosocial factors determine diet and physical activity behaviours and how do they contribute to differences in the risk of developing type 2 diabetes?

PH37/2 | What factors help or prevent hard-to-reach groups from being screened for active tuberculosis (TB): when it involves different service providers (for example, healthcare professionals, community workers) when it involves different settings and/or a different approach (for example, clinics, hospitals, detention centres, outreach, drop-in centres)?

PH37/3 | How effective and cost effective is tuberculosis (TB) testing (active and latent) for hard-to-reach groups when included as part of a broader health check (for example, blood-borne virus [BBV] screening)?

PH37/5 | How effective and cost effective is peer support as part of an enhanced case management (ECM) approach to ensuring hard-to-reach groups with active tuberculosis (TB) complete treatment? In particular, does effectiveness and cost effectiveness vary:
- according to the target population (that is, different hard-to-reach groups)
- by setting (for example, outreach versus clinic)
- by population (for example, age, gender, ethnicity)?

PH38/1 | Identification and monitoring:- Which combination of risk-assessment tools and blood tests (HbA1c or fasting plasma glucose [FPG]) are most cost effective and effective at identifying and assessing the risk of type 2 diabetes among populations at high risk? In addition, how frequently should testing take place to be efficient? How does effectiveness and cost effectiveness vary for different black and minority ethnic groups, for example, African-Caribbean and black African; people aged 18–40, people aged 75 and over, and for high-risk vulnerable adults?

PH38/2 | Identification and monitoring:- What are the demographic characteristics and rates of progression to type 2 diabetes among people with a high risk score but normal blood glucose levels (fasting plasma glucose of less than 5.5 mmol/l or HbA1c of less than 42 mmol/mol)? How does this compare with people who have both a high risk score and blood glucose levels that indicate impaired glucose regulation (fasting plasma glucose 5.5–6.9 mmol/l or HbA1c 42–47 mmol/mol (6.0–6.4%)?

PH38/3 | Identification and monitoring:- What are the most effective and cost-effective methods of increasing uptake of type 2 diabetes risk assessments and monitoring among those at greatest risk? Those at greatest risk include people from lower socioeconomic and black and minority ethnic groups, and those aged 75 or over.

PH38/4 | Lifestyle interventions:- Which components of an intensive lifestyle-change programme contribute most to the effectiveness and cost effectiveness of interventions to prevent or delay type 2 diabetes in those at high risk? How does this vary for different black and minority ethnic groups, for people of different ages for example, aged 18–24, 25–39 and 75 and over, and for vulnerable adults?

PH38/5 | Lifestyle interventions:- How effective and cost effective are different types of dietary regime in reducing short- and long-term blood glucose levels and preventing or delaying type 2 diabetes? How does this vary for different subgroups, for example, African-Caribbean and black African and other minority ethnic groups and for people of different ages, for example, aged 18–24, 25–39 and 75 and over?

PH38/6 | Lifestyle interventions:- How effective and cost effective are different types (and levels and frequency) of physical activity in reducing short- and long-term blood glucose levels and preventing or delaying type 2 diabetes? How does this vary for different subgroups, for example, different black and minority ethnic groups and people of different ages, for example, aged 18–24, 25–39 and 75 and over?

PH38/7 | Vulnerable groups:- What are the most effective and cost-effective methods for identifying, assessing and managing the risk of type 2 diabetes among high-risk, vulnerable adults? This group includes: frail older adults, homeless people, those with severe mental illness, learning or physical disabilities, prisoners, refugees, recent migrants and travellers.

PH39/2 | How prevalent is smokeless tobacco use among South Asian women who are pregnant and why? Is there a particular stage during pregnancy when smokeless tobacco is used? What impact does its use during pregnancy have on maternal and child health?

PH39/3 | What are the similarities and differences between smokeless tobacco and smoked tobacco in terms of chemical content and the harm that it can cause? Should interventions to help people quit smokeless tobacco differ from those used for smoked tobacco?

PH39/4 | How effective and cost effective are the following in terms of long-term (12 month) quit rates, and also for NHS standard, short-term quit rates (at 4 weeks and 6 months) for smokeless tobacco (confirmed by saliva cotinine test)?
- Pharmacotherapy combined with behavioural support and delivered by health professionals compared to brief advice, behavioural support or pharmacotherapy alone.
- Brief interventions (including brief advice) delivered by community members compared to brief interventions delivered by health professionals.
- Tobacco cessation services (including outreach services) that specifically focus on smokeless tobacco, compared to smokeless tobacco support provided by general tobacco cessation services.
- Training for health professionals (such as midwives, dentists and dental hygienists) to identify users of smokeless tobacco and raise awareness among them of the associated health risks.
- How does the effectiveness and cost effectiveness of the above differ by: age, gender and ethnic origin of the recipient; the status of the person delivering the intervention; the way it is delivered; its frequency, length and duration; and the setting in which it is delivered?

PH39/5 | Are there unintended consequences from encouraging people of South Asian origin to stop using smokeless tobacco (for example, do they experience more dental pain or start smoking more tobacco)?

PH39/6 | How strong are the cultural motivations (stemming from religion, tradition, media, and advertising) to use smokeless tobacco among people of South Asian origin? How do they compare with the physical addiction to nicotine? How might this information help in designing smokeless tobacco cessation programmes that are culturally appropriate?

PH39/7 | What components of an intervention or which general approaches work best in attracting people of South Asian origin to smokeless tobacco cessation services? How does this differ by age, gender and ethnic origin?

PH40/2 | How can the factors that pose a risk to, or protect, the social and emotional wellbeing of children aged under 5 years be identified and assessed to determine how children can benefit from different interventions?

PH40/4 | What types of home-based intervention are effective in promoting the social and emotional wellbeing of vulnerable children aged under 5 years without involving the parents? (This could include childcare provided by other family members or childminders.)

PH40/5 | How can interventions which have been proven effective in other countries be assessed for their cultural relevance to the UK? What measures should be used to assess how transferrable they are?

PH40/6 | What organisational mechanisms can ensure interventions to improve the social and emotional wellbeing and 'readiness for school' of vulnerable children aged under 5 years are effectively implemented? How do these differ according to the local context?

PH40/7 | What are the short, medium and long-term economic benefits of interventions aimed at developing the emotional and social skills of vulnerable, preschool children – for the individual, family and wider society? How should these be assessed?

PH40/8 | What indicators and datasets should be used to measure and predict social and emotional wellbeing over time? Which indicators and datasets can be used to assess the long-term benefits of interventions aimed at improving the social and emotional wellbeing of vulnerable children aged under 5 years?

PH41/4 | What key factors ensure people continue to walk or cycle in the long term (over a year)? How do individual interventions (such as follow-up or goal-setting) interact with environmental factors (such as distance, perception of danger or provision of facilities) in encouraging people to continue to walk or cycle?

PH41/5 | What key factors influence differences in walking and cycling behaviour among different groups – and what are the implications for interventions aiming to achieve population-level change and reduce inequalities?

PH42/1 | What is the most effective way to monitor and evaluate community-wide approaches to obesity to ensure:
1) evidence of effectiveness is gathered across the breadth of the local system and 2) data are produced to help local communities adapt and improve their approach?

PH43/1 | How can case-finding for hepatitis B and C be improved? What modifiable factors influence whether or not specific groups at increased risk of hepatitis B and hepatitis C infection are identified and tested?

PH43/6 | What are the most effective ways of involving people from groups at increased risk in awareness-raising about, and promoting testing and treatment for, hepatitis B and C infection? Specifically, how cost effective are peer mentor programmes at increasing the number of people at increased risk who are tested and treated for hepatitis B and C?

PH44/1 | How does the duration and frequency of brief advice influence its effectiveness and cost effectiveness? For example, do 'micro interventions' of less than 1–2 minutes have an impact on physical activity?

PH44/3 | What impact does the delivery of brief advice by different primary care practitioners – for example, GPs and practice nurses – have on physical activity? For example, is the perceived value of the information greater when provided by a particular primary care practitioner?

PH44/5 | How can brief advice be tailored to have the greatest impact on specific groups? For example, can it be tailored to meet the needs of people of a particular gender, socioeconomic status or with a particular disability?

PH44/7 | Are the Department of Health's 'Let's get moving' physical activity care pathway and the general practice physical activity questionnaire (GPPAQ) both commonly used in primary care? How do primary care practitioners view GPPAQ and, if they do not use it, why not?

PH44/8 | What infrastructures and systems help increase the number of assessments of physical activity undertaken and the delivery of brief advice? (Examples studied could include integration of brief advice into long-term disease management strategies, or the use of incentive strategies.)

PH45/1 | How effective are licensed nicotine-containing products when used for more than one year? What is the impact of different doses and duration of use? What is the effect on health of long-term use? What are smokers' and practitioners' views on long-term use?

PH45/3 | How effective are interventions to help people reduce the amount they smoke (without the intention of stopping)? How great are the health benefits of smoking reduction (by substituting some cigarettes with licensed nicotine-containing products) compared to stopping smoking? What proportion of people who reduce the amount they smoke go on to stop smoking? How soon after starting to reduce the amount they smoke do they stop completely?

PH45/4 | How effective are different behavioural strategies in helping people to cut down, either in order to stop smoking or to reduce the amount they smoke? This should include an evaluation of behavioural support used on its own and evaluations of specific components of such support (such as scheduling). It should also include evaluations of different types of behavioural support and follow-up, delivered within a clearly defined harm-reduction intervention.

PH45/5 | What impact do different marketing strategies, including mass-media campaigns, have on the number of people who adopt a harm-reduction approach? For example, compare the prices, placements and promotions for different types of licensed nicotine-containing product.

PH45/6 | Which harm-reduction approaches are smokers using and how do these correlate with smoking rates at the population level and among particular groups? For example, how do young people respond to the wider adoption of harm-reduction approaches? Do these approaches contribute to a continued reduction in smoking prevalence among young people, or does it make stopping smoking appear less important?

PH45/7 | What are the most effective methods of monitoring smoking status at the population level? This includes the development of biomarkers that can distinguish between nicotine use and smoking in order to validate these measures.

PH46/1 | What are the cut-off points for body mass index (BMI) among adults from black, Asian and other minority ethnic groups living in the UK that can be used to classify overweight and obesity or are 'risk equivalent' to the current thresholds in relation to mortality, cancer, type 2 diabetes, stroke and myocardial infarction set for white European populations? Ideally, prospective cohort studies should be used. Studies should use objectively measured height and weight and consider incidence as well as prevalence. Estimates should be adjusted for potential confounders.

PH46/2 | What are the cut-off points for waist circumference among adults from black, Asian and other minority ethnic groups living in the UK that are 'risk equivalent' to the current thresholds in relation to mortality, cancer, type 2 diabetes, stroke and myocardial infarction set for white European populations? Ideally, prospective cohort studies should be used. Studies should use objectively measured waist circumference and consider incidence as well as prevalence. Estimates should be adjusted for potential confounders.

PH46/3 | What are the corresponding cut-off points for waist circumference among adult males and females from black, Asian and other minority ethnic groups living in the UK, based on overweight and obesity BMI classifications?

PH46/5 | What are the risks and benefits of developing single-figure cut-off points on BMI and waist circumference for black, Asian and other minority ethnic groups to help prevent diabetes and other conditions?

PH46/7 | Are clinicians, practitioners and weight management service providers aware that black, Asian and other minority ethnic groups are at the same risk of type 2 diabetes and mortality at a lower BMI compared to the white population. If so do they intervene at lower BMI and waist circumference thresholds?

PH46/8 | How effective and cost effective are lifestyle interventions for people from black, Asian and other minority ethnic groups at different BMI and waist circumference thresholds, compared to the general population? Ideally this evidence should come from randomised controlled trials.

PH48/1 | How can interventions to increase the uptake and effectiveness of stop smoking interventions in acute, maternity and mental health settings be improved? (Examples include the identification and referral of smokers and staff training.) What components of an intervention help ensure someone will take up the support they are offered? How many people in these settings complete stop smoking treatment?

PH48/2 | How can the effectiveness and cost effectiveness (in terms of 4-week, 6- and 12-month quit and relapse rates) of intensive stop smoking interventions for people using mental health services be improved and tailored for this group? Does effectiveness or cost effectiveness differ by age, diagnosis, ethnicity, gender, inpatient or outpatient, sexual orientation or socioeconomic status? What type of training do health professionals need to deliver these interventions? Examples might include training to: build up knowledge related to tobacco dependence, its treatment and links with mental illness; develop skills in delivering support; develop a positive attitude towards delivering interventions.

PH48/3 | What is the effect and acceptability of approaches that aim to match nicotine dose (through licensed nicotine-containing products) to level of smoking addiction among women who are using maternity services?

PH48/4 | Are stop smoking interventions that include incentives to quit effective and cost effective for people using secondary care services, including women who are pregnant or have recently given birth?

PH49/1 | Which choice architecture interventions help to reduce increased-risk and higher-risk drinking of alcohol, improve sexual health behaviours, help stop or reduce smoking, or increase the physical activity levels of the general UK population? How is this related to sociodemographic variables?

PH49/2 | What evidence of effectiveness is there on the use of choice architecture interventions in commercial settings to influence health-related behaviours? How can findings from commercial settings support non-commercial choice architecture approaches to support behaviour change to improve health?

PH49/3 | Which combinations of behaviour change techniques and modes of delivery are effective and cost effective in initiating particular behaviour changes, and in maintaining those changes? How does this vary among people from different socio-demographic groups or with different levels of motivation, access to information or skills? Include research that builds the evidence base on the effectiveness of each behaviour change technique. For example, experimental and meta-analytic work could clarify which behaviour change techniques work when, and for whom.

PH49/4 | Which behaviour change interventions and programmes are effective and cost effective at changing multiple behaviours and maintaining behaviour change? How does this vary among people from different sociodemographic groups?

PH49/6 | How effective and cost effective are behaviour change interventions delivered remotely (that is, by telephone, text message, phone and tablet apps or the internet)? How does this vary among behaviours and among people from different sociodemographic groups?

PH49/7 | How do behaviour change techniques lead to change? What are the best methods of testing the relationship between the theories that describe change processes and the effectiveness of interventions in practice?

PH50/1 | How effective are programmes that aim to prevent domestic violence and abuse from ever happening in the first place? This includes media-based public health awareness campaigns. It also includes social movements to establish people's rights, and community-building and primary prevention activities that tackle underlying assumptions in society. (Examples of the latter might include the role and status of women.)

PH50/2 | How effective are combinations of interventions to deal with domestic violence and abuse in the short, medium and long term? Are the outcomes sustainable and do they have a beneficial effect on quality of life and health in the longer term?

PH50/3 | How effective are the following interventions in the short, medium and long term, across various levels of risk and including diverse and marginalised groups:
- advocacy
- domestic abuse recovery programmes
- perpetrator programmes
- psychological or social interventions modified for domestic violence and abuse, including programmes for those who have suffered multiple forms of abuse and those who are still experiencing it
- interventions for primary carers apart from mothers (for example, fathers, grandparents)
- interventions for other family members?

PH50/4 | What are the most appropriate ways to collect and manage data about domestic violence and abuse across the health, social care and criminal justice sectors? Is there value in collecting anonymised aggregate data, or is there a more useful method of data capture?

PH50/5 | What type of interventions (including training and referral pathways), in diverse health care settings, provide the most effective support for practitioners working with people who are experiencing, or have experienced, domestic violence and abuse?

PH51/1 | What are the most effective and cost effective ways to provide contraceptive services for socially disadvantaged young people to prevent unwanted pregnancies? In particular, what are the most effective and cost effective ways to provide contraceptive services for looked after children, those with learning difficulties, those who are not in education, employment or training or women who have had an abortion?

PH51/4 | What is the differential impact of interventions that aim to reduce unintended conception and abortion rates among young people aged under 25 years on subgroups of socially disadvantaged young people?

PH52/1 | How can needle and syringe programmes encourage specific groups of people who inject drugs to use the service effectively? Examples include: those who have recently started injecting; women; sex workers; ex-prisoners; people who are homeless; people who occasionally inject drugs; and people who inject novel psychoactive drugs.

PH52/3 | What type of behaviour-change interventions delivered by needle and syringe programmes are effective in promoting safer drug use practices and reducing the incidence of overdose (apart from providing needles, syringes and other injecting equipment)?

PH52/5 | Do needle and syringe programmes have any unintended consequences: Do they increase the uptake, frequency and length of injecting drug use? Does the provision of disposal facilities (for example, drop-boxes) affect the amount of drug-related litter in an area? Do they have a negative impact on the local community, for example, in terms of crime rates or the fear of crime?

PH53/1 | How effective are lifestyle weight management programmes available in the UK, when directly compared using high-quality trials? In particular, what effect do specific components of a multicomponent lifestyle weight management programme have on adherence, effectiveness and cost effectiveness? This includes:
- components, or combinations of components, that support weight loss or the prevention of weight regain
- the effect of programme length, intensity, setting and means of delivery (examples of the latter include group, individual and remote support)
- specific behaviour change techniques (using a recognised taxonomy)
- the effect of new technologies
- the effect of additional support services, such as self-help groups and networks approaches to commissioning
- processes for collecting long-term follow-up data.

PH53/2 | How effective and cost effective are lifestyle weight management programmes available in the UK over at least at least 3 to 5 years, and ideally beyond 10 years. Specifically:
- Do short-term (12-week) interventions provide adults with the self-management skills they need to maintain weight loss in the long term?
- Are alternative approaches to weight management (such as approaches that focus on a healthy lifestyle, behaviour change and the prevention of weight gain rather than weight loss) effective and cost effective in the long term?
- How effective and cost effective are programmes for people of different ages, gender, sexuality or from different ethnic or socioeconomic groups?
- How effective and cost effective are programmes for specific population groups, such as adults with depression or with disabilities?

PH53/4 | How can referrals to other services after involvement in a lifestyle weight management service be as effective and cost effective as possible? This includes: re-referrals to a lifestyle weight management service, referrals to other tiers of weight management services or referrals to other specialist services (such as alcohol or substance misuse). In particular:-
- How long should people wait before being re-referred to a programme?
- Does re-referral to the same (or a similar programme) influence adherence, effectiveness or cost effectiveness?
- In what circumstances should participants not be re-referred to the same (or a similar programme)?
- Who is best placed to provide ongoing support after the programme, and does this differ according to whether someone completed the programme or met their weight loss goal?
- Are there any unintended or adverse effects from repeated attempts to lose weight?

PH53/5 | What effect does lifestyle weight management training for health professionals and lifestyle weight management staff have on:
- The referral process, including patient satisfaction?
- Programme outcomes (weight loss and prevention of weight regain), adherence to the programme and participants' satisfaction with it?
- Staff confidence in discussing weight issues and any concerns about their own weight?
- Staff ability to deliver the programme?
- General approach of staff (that is, whether they adopt a 'respectful and nonjudgemental' approach as a result)?

PH54/1 | How effective and cost effective are different types of exercise referral scheme? Compare the relative effects of different models in controlled studies. Include health-related quality of life as an outcome. Compare exercise referral schemes that vary by:
- setting – for example, home-based, gym-based, community-based or outdoors
- intensity and duration – for example, a 12-week scheme involving 1 session a week, or a 6-week scheme involving 4 1-hour sessions per week
- the techniques used, for example, some use additional 'supportive' techniques such as 'motivational interviewing' and education sessions
- the target group, for example, people who are overweight and obese, people with raised blood pressure or cholesterol levels or those experiencing mild depression, anxiety or stress; or by age, gender, race or socioeconomic status
- other scheme characteristics including: design, content and delivery; referral mechanisms; choice of activity; cost and qualifications of instructors; and whether it is commissioned and delivered by an NHS, non-NHS or community-based organisation.

PH54/3 | What factors encourage under-represented groups to participate in and complete an exercise referral scheme? What factors prevent these groups from participating? Under-represented groups include: people from black and minority ethnic groups, people with disabilities and those from lower socioeconomic groups.

PH54/4 | What is the comparative effectiveness and cost effectiveness of exercise referral schemes compared with other interventions that aim to help people to become more physically active? Relative effectiveness and cost effectiveness should be compared in controlled trials.

PH55/3 | What community-based interventions are effective and cost effective at improving the uptake of, and reducing inequalities in the use of, dental services by groups of adults and children at high risk of poor oral health?

PH55/5 | What community-based interventions are effective and cost effective in improving dietary habits affecting the oral health of children and adults, and in particular those at high risk of poor oral health?

PH56/1 | How effective and cost effective are interventions to increase vitamin D access, uptake, adherence or status among identified at-risk groups? Does effectiveness vary by age, gender, ethnicity, socioeconomic or other specific population characteristics (such as depression or a disability)? The following could be considered:
- availability and uptake of supplements (including the impact of the cost of supplements)
- type of supplements provided and how that impacts on adherence
- knowledge and attitudes (of both the public and health and social care practitioners).

PH56/2 | How cost effective are preventive approaches to vitamin D deficiency among all at-risk groups, compared with the cost of testing and treatment? This should include a comparison of universal provision of free supplements with the provision of low or standard cost supplements for different at-risk groups. (If there is any new legislation allowing for the sale of Healthy Start supplements, this would provide an opportunity to test this question.)

SG1/1 | What is the relationship between the following factors and outcomes related to nursing care, patient safety and patients' and nursing staff satisfaction with the quality of care in the UK?
- Number of nursing staff
- Nursing skill mix
- Shift patterns

SG1/2 | How do the following factors affect the nursing staff requirement at ward level in the UK?
- Patient factors
- Patients' nursing needs (sometimes referred to as acuity and dependency)
- Time of day
- Ward layout and size (including the use of single rooms)
- Ward level team leadership and management
- Organisational training approaches
- Organisational policies and procedures (for example, productive ward, Lean)

TA214/1 | Further research designed to investigate differences in health-related quality of life and the clinical effectiveness of bevacizumab in subgroups, such as those with prior taxane exposure, would be particularly useful.

TA217/1 | Research is needed to generate robust and relevant data on the effects of treating people with Alzheimer’s disease on both short-term and long-term outcomes, disease progression through relevant health states, and quality of life.

TA217/2 | Research is needed on the impact of treating Alzheimer’s disease on mortality and institutionalisation, and to assess the relationship between disease progression and carer utility (quality of life).

TA222/1 | NICE proposes that a trial should be undertaken to compare the efficacy of trabectedin plus pegylated liposomal doxorubicin hydrochloride (PLDH) with platinum-based chemotherapy because this is the standard treatment in the platinum-sensitive population.

TA223/1 | A trial comparing the long-term effectiveness (beyond 24 weeks) of cilostazol, naftidrofuryl oxalate, pentoxifylline and inositol nicotinate and placebo would be beneficial. It should collect utility data as well as walking distance outcomes.

TA235/1 | Further studies on the clinical effectiveness of mifamurtide when combined with the chemotherapy typical of UK clinical practice would be useful to determine the size of the effect of mifamurtide.

TA235/2 | Further collection of quality of life data from people who are cured and who have experience of amputation and chemotherapy are also needed. Additional data on the health effects on parents, siblings and others with life-threatening illness would also be of value.

TA244/1 | NICE recommends that a study is conducted to generate robust evidence about the benefits of roflumilast as an add-on to LAMA plus LABA/ICS or LAMA plus LABA for those people who are intolerant to ICS.

TA245/1 | More trials of apixaban compared with other low molecular weight heparin (LMWHs) in total hip and knee replacement would decrease the uncertainty of the clinical and cost effectiveness of these treatments. Trials directly comparing apixaban with rivaroxaban, dabigatran etexilate and fondaparinux would strengthen the evidence base for these comparisons.

TA254/2 | NICE recommends that a new model for multiple sclerosis is developed, ideally based on UK patient cohorts, which uses the best available evidence (including experience to date from the risk-sharing scheme) and includes all currently available treatments.

TA271/1 | Further research to resolve uncertainties about the cost effectiveness of fluocinolone acetonide intravitreal implant for the treatment of chronic diabetic macular oedema is recommended. This should focus on a group of patients whose condition is unresponsive to other available therapies, and include measures of efficacy and health-related quality of life.

TA272/1 | Research on second-line treatments for transitional cell carcinoma of the urothelial tract is needed. It noted that the vinflunine studies were the only studies in patients with transitional cell carcinoma of the urothelial tract whose disease had progressed after platinum-based chemotherapy. It was noted that there is a lack of evidence for the relative effectiveness of treatment options at this stage in the pathway of care. It is recommended that studies be undertaken to investigate the relative safety and efficacy of second-line treatments for transitional cell carcinoma of the urothelial tract, particularly randomised controlled trials.

TA275/1 | There is a need for additional research on the management of bleeds that occur while people are receiving apixaban, rivaroxaban or dabigatran etexilate, as there are no antidotes or established treatments to stop active bleeding for these agents.

TA283/1 | NICE concluded that further research directly comparing the clinical and cost effectiveness of ranibizumab and bevacizumab in people with macular oedema secondary to retinal vein occlusion should be conducted.

TA287/1 | There have been no head-to-head trials of rivaroxaban compared with a low molecular weight heparin for people who have cancer and experience an acute pulmonary embolism or deep vein thrombosis. As in NICE technology appraisal guidance 261 it is recommended that further research should be carried out.

TA293/2 | NICE recommends research generating and analysing observational data including, but not limited to, the existing UK ITP Registry, which collects data on the long-term outcomes of patients treated with eltrombopag and romiplostim.

TA299/1 | It is a condition of the marketing authorisation for bosutinib that a single open-label multicentre efficacy and safety study is conducted of bosutinib in patients with Philadelphia-chromosome-positive chronic myeloid leukaemia previously treated with 1 or more tyrosine kinase inhibitor(s) and for whom imatinib, nilotinib and dasatinib are not considered appropriate treatment options.

TA301/1 | Further research is recommended to resolve uncertainties about the cost effectiveness of fluocinolone acetonide intravitreal implant for the treatment of chronic diabetic macular oedema. This should focus on a group of patients whose condition is unresponsive to other available therapies, and include measures of efficacy and health-related quality of life. Research should focus on identifying appropriate utility values, taking into account the utility values for different levels of visual acuity and the relative relationship in utility values from treating the best-seeing and the worse-seeing eye. The appropriateness of generalising utility values from one group of eye conditions to another group would also be of value.

TA304/2 | NICE recommended the collection of data on prosthesis failure or on the prevalence of people living with a failed hip but for whom revision surgery is not suitable or who choose not to have revision surgery. NICE further recommended that nomenclature for hip replacement failure needs to be established to allow demarcation of prosthesis-dependent and prosthesisindependent hip replacement failure. Furthermore, patient reported outcome measures collected as part of the National Joint Registry should allow for reporting of hip replacement failure in people who cannot or choose not to have revision surgery.

TA313/1 | NICE considered that there is an important need for head-to-head comparisons between biological treatments for psoriatic arthritis, particularly in people for whom treatment with tumour necrosis factor (TNF) alpha inhibitors has been unsuccessful.

TA316/2 | NICE considered that if enzalutamide is used in routine clinical practice for treating hormone relapsed metastatic prostate cancer that has been previously treated with abiraterone, data should be collected on resource use and overall survival.

TA319/2 | Further research into whether concomitant dacarbazine enhances the clinical effectiveness of ipilimumab would be encouraged because it could provide information for future treatment strategies, as would more data on the relative effectiveness of ipilimumab when given as a first-line or second-line treatment.

TA320/1 | NICE recommends further research to better inform future cost-effectiveness models of relapsing-remitting multiple sclerosis. In particular, this research should include a more comprehensive synthesis of available evidence on the underlying disease progression of multiple sclerosis in the UK context, the impact of disability and relapses on preference-based measures of quality of life, and associated resource use and costs.

TA322/1 | NICE noted that the cost effectiveness of lenalidomide compared with standard care for people with low- or intermediate-1-risk MDS associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate, was sensitive to whether the patient access scheme would be realised in clinical practice. The Committee agreed that it would be critical to generate evidence to support the following:
- The proportion of people who become eligible for the patient access scheme, that is, that they remain on treatment beyond 26 cycles.
- The benefit of lenalidomide after 26 cycles, that is the associated overall survival and health related quality of life for those who remain on treatment beyond 26 cycles.